Journal of Pathology and Translational Medicine

Original Articles

The Study of Proliferating Cell Nuclear Antigen in Colorectal Carcinoma.: Ho Soo Choi, Bok Soog Yang, Ji Shin Lee, Min Cheol Lee; Korean J Pathol. 1995;29(3):311-320.

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Abstract PDF: The determination of proliferative activity in the colorectal mucosa has been used for different purposes as the estimation of cancer risk and the assessment of disease activity in ulcerative colitis. But the prognostic significance of proliferative activity in colorectal carcinomas remains controversial. To investigate the prognostic significance of proliferative activity in colorectal carcinomas, the author estimated the proliferative activity immunohisto chemically using the monoclonal antibody PCNA and compared with clinicopathological data in 62 colorectal carcinomas. The results were as follows: 1) The reactivity of PCNA was more pronounced at the infiltrative margins of the tumors and tumor cells within the vascular or lymphatic channels. 2) The mean PCNA index of colorectal carcinomas was 40.5?0.4%. PCNA indices had positive correlations with lymph node invasion(p<0.05), liver, metastasis(p<0.05), Dukes' stage(p<0.01) and TNM classification(p<0.01), and didn't correlated with location of tumor, size of tumor, histological type and lymphtic or vascular invasion. 3) The patients with high PCNA index(more than 45%) represented higher recurrence or metastasis rate(37.5%) than those with low PCNA index (less than 45%)(19.3%) in Dukes B or C colorectal carcinomas during the follow-up periods, but not significant statistically. These results suggested that the reactivity of PCNA may be a useful prognostic factors in colorectal carcinomas.

Histologic and Immunohistochemical Study of Cutaneous Vascular Disorders.: Jai Hyang Go, Hoon Jin, Dong Hwan Shin, Kwang Gil Lee; Korean J Pathol. 1995;29(3):327-333.

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Abstract PDF: There is a wide array of designation for cutaneous vascular disorders based on clinical characteristics, histology, embryology, cellular biology, and hemodynamics. The cutaneous vascular disorders can be divided into hemangioma and vascular malformation according to the biologic classification based on cell kinetics i.e. endothelial hyperplasia. There are clinical and histologic differences between them. In this study, clinical, histologic and im-munohistochemical evaluations were attempted on 40 cases of cutaneous vascular disorders diagnosed the period between 1985 and 1993. The results are as follows: 1) Twenty-three out of forty cases were immunoreacive for proliferating cell nuclear antigen(PCNA). The lesions composed of capillary-sized blood vessels with endothelial hyperplasia were diffusely reactive, whereas those composed largely of dilated blood vessels with or without focal endothelial hyperplasia were only focally reactive. 2) Each groups of the classic classification contained both reactive and nonreactive cases except nevus flammeus and juvenfle hemangioma. 3) In contrast to the cases nonreactive for PCNA, those reactive for PCNA contained areas of proliferating small vessels, which showed reactivity for PCNA. In conclusion, the cutaneous vascular disorders diagnosed by the classic classification are heterogeneous in the pattern of the endothelial hyperplasia and the PCNA staining. Therefore it should be classified by the clinical and the histologic characteristics.

AgNOR Counts in S-phase Human Cells.: Seung Il Kim, Eun Jung Lee; Korean J Pathol. 1999;33(2):103-107.

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Abstract: The nucleolus of human cell is a morphologically well recognizable nuclear organelle and the argyrophilic NORs (AgNORs) are nucleic acid-argyrophilic nonhistone protein complex in the nucleoli and the silver staining allows their identification and enumeration at the light microscopic level. The AgNOR counts are in parallel with mitotic activity and vary in different phase of cell cycle. It has been reported that human cells have one AgNOR during interphase and S-phase. However, the correlation between the number of AgNORs and S-phase markers is still controversial and they have never been studied simultaneously. In this study, AgNOR and PCNA were stained simultaneously to find out the relationship of AgNOR counts with cell cycle (S-phase) in human palatine tonsil, gastric carcinoma, liver and brain tissues. S-phase cells (PCNA-positive) were found predominantly in lymphoid follicles in palatine tonsil but gastric carcinoma showed diffuse immunoreactivity for PCNA. The AgNOR counts varied according to the type and locus of tissue. More than one AgNOR were identified in S-phase cells and some of hepatocytes and neurons in the brain which were not in S-phase contained two or more AgNORs. The above results suggest that the number of AgNOR is a characteristic feature of each type of cells and can be more than one even in S-phase.

The Correlation between the Proliferative Activity in Biopsied Specimen of Gastric Adenocarcinoma and the Pathologic Findings of Resected Specimen.: Hye Sun Kim, Jae Bok Lee, Se Min Kim, Jong Sang Choi, Han Kyeom Kim; Korean J Pathol. 1997;31(3):211-218.

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Abstract PDF: Studies on the correlation between proliferative activity of biopsied specimen and pathologic findings of resected specimen have been carried out to find the prognostic factors. To estimate the proliferative activity, 100 cases of biopsied specimen of gastric adenocarcinoma were tested for the PCNA (proliferating cell nuclear antigen) and the AgNOR (argyrophilic nucleolar organizer region) by the immunohistochemical and histochemical stainings, respectively. The resected tumors classified by histologic type, differentiation, depth of invasion, and nodal metastatic status were followed by cell cycle analysis using flow cytometry. The PCNA LI (labelling index) were higher in well or moderately differentiated tumors (P<0.01) than the poorly differentiated ones and the aneuploid tumors (P<0.05) more than in diploid ones. However, there were no correlations among histologic types, depth of invasion, nodal metastatic status and PCNA LI. The AgNOR counts were higher in advanced tumor than in the EGC (early gastric cancer) (P<0.01). In cases with nodal metastasis, most of them showed the AgNOR counts higher than those without nodal metastasis. There were no correlations between the AgNOR counts and the DNA ploidy, histologic type, or differentiation. High PCNA LI and high AgNOR counts were shown in cases with advanced tumors (P=0.000) and nodal metastasis (P<0.05). No correlation was shown with the histologic type or differentiation. The results show that proliferative activity of the biopsied specimen of gastric adenocarcinoma is correlated with the differentiation and the invasion depth of resected specimen. Especially, better correlation is obtained by analyzing both the PCNA LI and the AgNOR counts than by analyzing each.

A Study of the Relationship between p53 Mutation and Proliferating Activities in Astrocytic Tumors.: Geun Ho Lee, Jong Sang Choi; Korean J Pathol. 1999;33(3):158-168.

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Abstract PDF: To evaluate the relationship between p53 protein expression and proliferating activity in astrocytic tumors, we performed a study using 37 cases of astrocytic tumors; 13 cases of low-grade astrocytoma (LGA), 9 cases of anaplastic astrocytoma (ANA), and 15 cases of glioblastoma multiforme (GM). The p53 protein expression was studied by immunohistochemical staining (IHC) with DO-7 monoclonal antibody in 37 cases and p53 mutation was detected by single strand conformational polymorphism (SSCP) using PCR products of 31 cases. Proliferating activities were detected by Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA). Immunohistochemically, 24.3% (9/37) of astrocytic neoplasms showed p53 expression, which consisted of 7.7% (1/13) of LGA, 44.4% (4/9) of ANA, and 26.7% (4/15) of GM. The p53 expression was statistically significant between the tumor grades. p53 mutations on exon 5 were noted in 6 (19.4%) out of 31 cases of astrocytic tumors. Average indices of MIB-1 and PCNA were 1.5 2.6% and 7.0 10.1% in LGA, 10.0 12.7% and 23.7 23.2% in ANA, and 30.9 22.4% and 69.9 26.7% in GM, respectively. p53 positive group by IHC showed significantly higher average MIB-1 (26.2 23.5%) and PCNA index (56.7 30.3%) than those (12.1 18.3%, 27.6 29.6%) of p53 negative group (p<0.05). p53 mutation group also showed significantly higher MIB-1 (30.7 26.0%) and PCNA index (55.5 32.6%) than those without p53 mutation (10.8 16.5%, 24.2 28.7% respectively). These results showed that about one-fifth of astrocytic tumors have p53 abnormalities, which were related with higher proliferating activities than those without p53 abnormalities.

The Prognostic Significance of p53 Protein and PCNA in Advanced Gastric Carcinoma.: Ho Won Hwang, Hyung Bae Moon; Korean J Pathol. 1995;29(4):450-458.

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Abstract PDF: The 5 year-survival rates were examined to evaluate the prognositic significance of the expression of the p53 protein and the positivity of the PCNA in 108 cases of advanced gastric carcinoma. The p53 protein and PCNA were stained by immunohistochemistry in the tissue of the gastrectomized specimen. The results were as follows. 1) The overall 5 year-survival rate of advanced gastric carcinoma was 42.3 % and the significant prognostic factors were a pathologic stage and p53 protein(p<0.005). 2) The expanding or infiltrating type by Ming's classification and the intestinal or difftise type by Lauren's classification had similar prognosis. 514_ @@l %R-t 3) The 5 year-survival rate of the p53-positive group was 25.1% and that of p53-negative group was 56.1%(p<0.005). 4) The 5 year-survival rate of the PCNA low-grade tumors by PCNA stain(<50%)was 48.7% and that of the high-grade tumor(>=50%)was 29.9%(p>0.1). 5) There was a tendency to have a good prognosis in the p53-negative group and low grade tumors in the stage 11, III, and IV. There was a significant difference between p53 protein positive and negative groups in the stage III(p<0.005), but no significant differences were found in the other groups. The above results indicate that the p53 protein is an another useful tool for prediction of the prognosis in advanced gastric carcinoma.

Immunohistochemical Investigation on Expression of Hepatitis B Surface Antigen, Transforming Growth Factor-alpha, and Proliferating Cell Nuclear Antigen in Hepatocellular Carcinoma.: Bang Hur, Man Ha Hur; Korean J Pathol. 1995;29(4):478-491.

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Abstract PDF: In an attempt to evaluate the expression of hepatitis B surface antigen(HBs Ag), transforming growth factor-ct(TGF-alpha), and proliferating cell nuclear antigen(PCNA) in hepatocellular carcinoma(HCC), an immunohistochemical investigation(ABC method) was performed using 31 surgically resected HCCS. The authors examined the expression rate and patterns, histopathologic correlation, and inter-relationships among these expressions. The results were summarized as follows. 1) Among 25 seropositive HCCS, 15 cases showed tissue expression of HBs Ag(60.0%), being expressed as a predominantly cytoplasmic pattern. Its expression rate in low grade HCC was significantly high(76.9%), in contrast to a low rate in high grade HCC(41.7%)(P<0.05). Adjacent nonenoplatic tissue showed a higher expression rate(82.6%). 2) TGF-alpha was expressed in 23 of 31 cases of HCC(74.3%). The intensity and extent of its expression did not correlate tyros with histopathologic features. Bile duct epithelium, juxtaposed and/or entrapped liver cells, and cirrhotic nodules were variably expressed, of which intense peripheral reaction within the nodules was frequently noted. 3) PCNA was expressed throughout the neoplastic tissue of HCC. Its index was significantly high(34.4 13.6), being compared to low index index(3.5 2. 1) in the nonneoplastic tissue(P<0.005). High grade tumors revealed a higher index than the low grade tumors(P<0.05). Conclusively, this data confirms that PCNA index offers useful information about cell proliferation associated with histologic degrees of malignancy of HCC, albeit TGF-alpha is also involved in cellular proliferation of both liver cell and bile duct epithelium. Changes in incidence and cellular localization of HBs Ag expression between the neoplastic and nonneoplastic tissues suggest that an integrated viral genome could be functionally altered during hepatocarcinogenesis. A significant inter-relationship among these expressions was not observed.

DNA ploidy and Cellular Proliferation Activity in Experimentally Induced Malignant Fibrous Histiocytoma.: Ji Shin Lee, Jong Tae Park, Sang Woo Juhng, Hong Ran Choi, Kyu Hyuk Cho; Korean J Pathol. 1993;27(3):205-216.

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Abstract PDF: To fine out the changes of DNA ploidy and cellular proliferation activity during carcinogenesis and evaluate correlation between flow cytometrically determined S-phase fraction and proportion of proliferation cell nuclear antigen(PCNA, PC10) immunoreactive cells, the authors studied on malignant fibrous histocytoma induced by intra-articular injection of 9, 10-dimethy1-1, 2-benzanthracene(DMBA) in the rats. Forty Wistar rats were used. The results obtained were as follows. 1) Firstly, tumors were palpated 5 weeks after the last injection of DMBA and formed in 27 rats at sacrificed. Histologically, these lesions showed storiform, indicative of malignant fibrous histiocytoma. 2) Three cases of DNA aneuploidy were observed at 4 and 5 months after the last injection of DBMA and one of them, which was DNA diploidy at main mass, was found at daughter mass. 3) Flow cytometrically determined S-phase fraction and proportion of PCNA(PC10) immunoreactive cells in malignant fibrous histiocytoma induced by DMBA were much higher than in control groups and slightly increased according to sequential changes after formation of mass. The comparison of flow cytometrically determined S-phase fraction and proportion of PCNA(PC10) immunoreactive cells showed significant correlation(r=0.6092, p<0.001). Above results strongly suggest that ploidy pattern may evolve into aneuploid type during the development of tumor and proliferation activity increases during the carcinogenesis.

Expression of CDK 4, Connexin 32, and PCNA in N-diethylnitrosamine-Induced Lesions of Rat Liver.: Bang Hur, Hung Jun Kim; Korean J Pathol. 1999;33(5):309-318.

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Abstract PDF: Cellular altered foci (CAF), hyperplastic nodules (HN) including regenerating and adenomatous nodules, and hepatocellular carcinomas (HCC) were induced in Sprague-Dawley rat liver by prolonged administration of N-diethylnitrosamine (DEN, 200 ppm). Immunohistochemical expression of connexin 32 (Cx 32), cyclin-dependent kinase 4 (CDK 4), and proliferating cell nuclear antigen (PCNA) was assessed for the evaluation of preneoplastic potential of CAF. Regardless the duration of DEN administration, basophilic cell foci were the most frequently observed lesion in both CAF and cellular expanding hyperplastic nodules. Eosinophilic cell foci, however, were concomitantly increased with adenomatous nodules in later experimental groups. Cx 32 showed perimembranous spot-like expression. Its number was 7.25 2.10 per cell in normal hepatocytes. CAF and adenomatous nodules showed markedly decreased Cx 32 spots. Moreover, its reduction was more prominent in HCC. PCNA-labelled hepatocytes were scattered in the most CAF, showing no significant difference between each CAF. PCNA labelling index (LI) in adenomatous nodule and HCC was markedly increased. CDK 4 was localized in the cytoplasm and/or nucleus of hepatocytes. Eosinophilic cell foci revealed more nuclear expression of CDK 4 than other types of CAF, of which expression incidence was comparable to that of adenomatous nodule. Nuclear CDK 4 expression in HN and HCC was increased, although significant difference between regenerating nodule and adenomatous nodule was not seen. In conclusion, the incidence of CDK 4 was concomitantly increased with PCNA LI, however, reciprocally decreased with Cx 32 in accordance with the advance of DEN-induced HCC in rat. Phenotypically altered foci manifested as CAF are early valuable preneoplastic marker lesion for evaluation. In addition, basophilic cell foci can be considered a discernible marker of cellular expansion within nodules. However, eosinophilic cell foci might be an indeterminate marker for the advance of DEN-induced HCC in rat.

Correlation between Tumor Angiogenesis (Microvessel Density), Metastasis and Tumor Cell Proliferation in Colorectal Carcinomas.: Young Chae Chu, Joon Mee Kim; Korean J Pathol. 1997;31(6):517-526.

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Abstract PDF: Tumor angiogenesis has been shown to be associated with metastatic potentials in breast, lung and prostatic carcinomas. The relation between tumor angiogenesis and metastatic potentials in colorectal cancer has not been established to date. We analysed 66 selected patients with colorectal carcinomas (37 with and 29 without nodal metastases) for the microvessel density, tumor proliferation activity, and the clinicopathologic parameters including size, stage, histologic grade, growth pattern, presence of angioinvasion, perineural invasion and lymph node metastasis. For evaluation of microvessel density and tumor proliferative activity, the primary tumors were immunohistochemically stained for CD31 and PCNA. The mean microvessel counts (MVC) per 200X field were 99.27+/-23.28 and 131.35+/-31.48 in node-negative and node-positive patients, respectively. The PCNA index was 39.41+/-5.63% and 56.60+/-7.09% in node-negative and node-positive patients, respectively. MVC and PCNA index were higher in tumors with nodal metastasis (p=0.002, p<0.001), and also correlated each other (sr=0.33, p=0.007). Higher microvessel counts were seen in tumors with advanced stage (p=0.016). Tumor proliferation activity assessed by PCNA immunostaining was significantly higher in tumors with advanced stage, perineural invasion, angioinvasion, poor differentiation and larger size. From these results, MVC and PCNA index in colorectal carcinomas are assumed to be valuable prognostic parameters. Thus assessment of tumor angiogenesis and tumor cell proliferation in colorectal carcinomas may be helpful for the patients in need of aggressive therapy.

A Study on the Expression of p53 Oncogene Products, PCNA Index and DNA Ploidy in Renal Cell Carcinoma.: Jong Jae Jung, Ji Shin Lee, Chan Choi; Korean J Pathol. 1997;31(7):672-682.

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Abstract PDF: Mutant p53 is associated with the advanced stages of some human tumor but there is a wide variation in the reported incidence of p53 mutation in renal cell carcinoma and its prognostic significances. We designed this study to assess the expression of p53 in renal cell carcinomas and to compare with the established prognostic factors. Immunoreactivity for p53 protein and proliferating cell nuclear antigen (PCNA) were assessed in 44 cases of primary renal cell carcinoma, and flow cytometric analysis of DNA ploidy was perfon-ned in 37 of those cases. p53 protein was over-expressed in 16/44 (36.4%) renal cell carcinomas and 5 rumors had more than 10 immunoreactive tumor cells. The expression of p53 protein was positively related to nuclear grade (p=0.007) and PCNA index (p=0.002), but was independent of stage and DNA ploidy. In univariate survival analysis, stage (p<0.001), nuclear grade (p=0.017), DNA ploidy (p=0.045) and PCNA index (p<0.001) were significantly associated with patient survival. However, considering the stage, all of the last three factors had no prognostic influence. Cases showing strong positivity of p53 expression had worse prognosis than those with no or weak p53 expression, especially in early lesions (stage I,II) (p<0.001).

An Immunohistochemical Study of the Relationships between Estrogen and Progesterone Receptors and Proliferating Cell Nuclear Antigen in Endometrial Hyperplasia and Adenocarcinoma.: Seol Mi Park, Hye Kyoung Yoon, Jong Eun Joo; Korean J Pathol. 1996;30(1):15-22.

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Abstract PDF: Estrogen and progesterone receptors exist in the epithelial and stromal cells of the endometrium. Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions of estrogen and progesterone in epithelial and stromal cells. This study was performed to evaluate the differences estrogen and progesterone receptor(ER/PR) expression in the epithelial and stromal cells of endometrial hyperplasias and adenocarcinomas using immunohistochemical methods. Immunohistochemical analysis of proliferating cell nuclear antigen(PCNA) was done to evaluate a possible correlation between PCNA and hormone receptor expression. Evaluation was based on samples from 31 simple hyperplasias, 30 complex hyperplasias, and 32 adenocarcinomas. The immunohistochemical expression of ER, PR and PCNA in epithelial and stromal cells were examined according to a scoring system based on the percentage of positive cells and the staining intensity. The results were as follows; 1) The expression of ER and PR in epithelial cells showed a graded, significant decreases in simple hyperplasia, complex hyperplasia and endometrial carcinoma, in that order(ER: P=0.008, PR: P= 0.026). 2) PR expression in the stromal cells showed a significant decrease between hyperplasia and adenocarcinoma(P=0.003). The difference in ER expression was not significant. 3) In stromal cells, the decrease in PR expression was more prominent than the decrease in ER expression when complex hyperplasia was compared to simple hyperplasia. 4) The PCNA expression in simple and complex hyperplasia and adenocarcinoma was not higher than the expression of PCNA in nomal proliferative endometrium. There was no significant difference in PCNA expression between simple and complex hyperplasia and adenocarcinoma(P=0.073). 5) A negative correlation between PCNA and ER/PR expression was not demonstrated in simple and complex hyperplasia, or in adenocarcinoma. Endometrial hyperplasia and adenocarcinoma are probably related to a paracrine action of estrogen and progesterone in epithelial and stromal cells. A progressive loss of PR expression in stromal cells may induce abnormal proliferation of endometrium due to a disrupted hormonal balance.

Correlation between Nuclear Grades and the Numbers of AgNORs and PCNA Labeling Indices in Renal Cell Carcinoma.: Hye Jin Lee, Young Im Han, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1996;30(2):132-139.

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Abstract PDF: The author examined the number of AgNORs and PCNA labeling indices by histochemical and immunohistochemical studies in 20 cases of renal cell carcinoma, composed of 5 cases according to the nuclear grades. The results obtained are summarized as follows; 1) Mean number of AgNORs according to the nuclear grades of renal cell carcinoma were 1.38+/-0.40 (mean+/-standard deviation) for Grade I, 2.53+/-0.33 for Grade II, 5.43+/-0.66 for Grade III, and 7.88+/-0.72 for Grade IV. The mean numbers of AgNORs according to the nuclear grades were significantly increased(p=0.0005). 2) PCNA labeling indices (positive nuclear ratio) according to the nuclear grades of renal cell carcinoma were 5.90+/-2.36 for Grade I, 19.30+/-6.71 for Grade II, 45.73+/-8.62 for Grade III, and 61.83+/-6.34 for Grade IV. Also, the PCNA labeling indices according to the nuclear grades were significantly increased(p=0.0008). 3) The mean numbers of AgNORs directly correlated with the PCNA labeling indices (r=0.9861, p<0.001). On the basis of the above results, it was considered that the numbers of AgNORs and PCNA labeling indices as markers of proliferative activity of tumor cells correlate well with the nuclear grades of renal cell carcinoma.

Immunohistochemical Analysis of Estrogen Receptors and Progesterone Receptors in Leiomyoma of Uterus Compared with PCNA Index.: Jung Ran Kim; Korean J Pathol. 1996;30(2):140-149.

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Abstract PDF: Estrogen receptor(ER) and progesterone receptor(PR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in leiomyomas and myometrium from same patients from 38 women in various stages of the menstrual cycle, menopause and pregnancy. Two postpartum uteri are also included. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution, and the results were compared with those of PCNA index. In all samples, ER and PR localized within the nuclei of target cells. The histochemical score of ER in leiomyoma was significantly greater than that found in myometrium. But ER in leiomyoma was expressed in cyclic fashion(r=0.45, P=0.006), like as in myometrium, throughout the menstrual cycle, paralleled by a concomitant, though delayed. In contrast, PR content constantly maintained in myometrium and leiomyoma throughout menstrual cycle, and there was no significant difference between them. However, leiomyoma and myometrium of pregnancy showed a significant reduction in the amount of ER and PR localized. PCNA index in leiomyoma(14.9+/-24.4) was also significantly higher than that found in myometrium(2.1+/-3.3). The index declined throughout the secretory phase. The leiomyoma had increased PCNA index during pregnancy, while the increasing rate in leiomyoma was lower than that of myometrium. The growth potential of leiomyomas is appearently higher than that of myometrium under the high progesterone level. The most of neoplasm with high PCNA index(10 above) contained absolute or relative abundant PR or ER content. Alteration of receptor content may be an important mechanism in steroid dependent growth of leiomyoma and may provide information useful in the clinical management of this neoplastic disorder.

Comparative Study

A Comparative Study of PCNA Immunostaining, AgNOR Scores Hormone Receptors and Histology in Human Breast Cancer.: Eun Sook Chang, Kwan Kyu Park; Korean J Pathol. 1993;27(6):605-617.

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Abstract PDF: This study was performed on 50 cases of primary breast cancer removed surgically during the period 1990~1991 and compared the results of four morphologic methods developed for the detection of estrogen receptors, progesterone receptors, monoclonal antibody PCNA immunoreactivity, and the mean number of argyrophilic nucleolar organizer regions(mAgNORs) to ascertain the prognostic significance and also to detect highly malignant heterogenous cancer. To determine the validity of these measurements, a variance analysis was done with Kruskal-Wallis 1-way ANOVA. The results showed that the significant correlation between histologic grade and ER/PR status(P=0.005/P=0.015), the borderline significant correlation between mAgNORs and ER/PR status(P=0.08), and between AgNORs and stage(P=0.07), PCNA has no correlation with ER/PR status(P=0.25), clinical stage and histologic grade. In follow up, four cases of invasive ductal carcinoma with ER/PR, developed early and rapid metastasis within 2 years, three of them were classified as histologic grade 3 and another case was grade 2, whereas two of them were classified ans stage III(+) and the rest were in stage IIB(+) and stage IIA(-). The mAgNOR count of these four cases were ranged from 3.32 to 4.29 which were in the aneuploid category most likely. One of them had rather stormy rapid course with multiple organ metastases resulting death within one year. These results indicated that ductal carcinoma(>2cm size) with ER-/PR- and high mAgNOR level or high PCNA grade, and hihg histologic grade had h highly malignant course, marked by rapidly developing metastases. Thus we concluded that the status of ER/PR alone in tumor tissue is an important information for selecting hormone treatment btu, for the ultimate prognosis, is a weak indicator. Therefore for early detection of such heterogenous tumor, besides ER/PR, AgNORs or PCNA, histologic grade and tumor size are very useful as biological indicators of prognosis. The status ER/PR in combination with these indicators are more accurate and provide better basis on which to base a decision for early implementation of chemotherapy from which to give probably benefit by inhibition of rapid progress.

Original Articles

Expression of Apoptosis, bcl-2, and PCNA in Uterine Cervical Intraepithelial Neoplasia and Invasive Carcinoma.: Myoung Ja Chung, Kyu Yun Jang, Myoung Jae Kang, Dong Geen Lee, Byung Chan Oh; Korean J Pathol. 1997;31(11):1180-1189.

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Abstract: This study was undertaken to know the extent of apoptosis, expression of bcl-2 and proliferating cell nuclear antigen (PCNA) in uterine cervical intraepithelial neoplasia (CIN; 15 cases) and invasive carcinoma (27 cases) and to evaluate them as a prognostic marker. Apoptosis was analysed by using the in situ apoptosis detection kit and bcl-2 and PCNA were detected by the immunohistochemical method. The results were as follows: Apoptotic indices (AI) in the invasive carcinoma (mean: 4.3) were 10-times higher than that in the CIN (mean: 0.43). Bcl-2 was expressed 60% of the cases in the dysplastic cells of the CIN II and CIN III, 33.3% of cases in the invasive carcinoma and not expressed in the CIN I except basal cells. The expression of the PCNA was increased by the grades of CIN and was strong in invasive carcinoma. The mean survival time of the patient with invasive carcinoma was significantly decreased in the higher AI index (above 4.3) than in the lower AI index (below 4.3). There was no significant correlation between the extent of apoptosis and the expression of bcl-2. According to the above results, AI are able to be used as an independent prognostic marker in the invasive cervical carcinoma, and bcl-2 and PCNA have an important role in the tumorigenesis of uterine cervical carcinoma.

Histologic Grading of Astrocytic Neoplasms in Conjunction with Evaluation of Proliferative Activity Using Ag-NORs Count PCNA Expression, and Flow CYtometric DNA Analysis.: Mee Yon Cho, Soon Hee Jung, Tal Seung Kim, Yong Pyo Han; Korean J Pathol. 1994;28(1):49-55.

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Abstract PDF: Although the histologic grade of astrocytic neoplasms of the brain have been used as a prognostic factor, the lack of an objective criteria is possible to create the disagreement of classification. We evaluated 25 cases of astrocytic neoplasms of brain to document the usefulness of prolifera-tive potential of tumor as a prognostic indicator and the correlation with histologic grade by Nils Ringertz. The Ringertz's classification was relatively simple in an application among the variable systems and easy to define the differentiate from grade to grade. The examined cases were com-prised of 7 astrocytomas, 9 anaplastic astrocytomas and 9 glioblastoma multif6rmes. The prolife-rative potential of tumors were measured by Ag-NORs count, PCNA labeling index and flow cytometric analysis. The mean numbers of Ag-NORs per cell and PCNA labeling index were sig-nificantly differ among each histologic grade. In addition, abnormal DNA content and high prolif-erative index were frequently identified in anaplastic astrocytoma and glioblastoma multiforme. Therefore, the Ag-NORs counts, PCNA labeling index, DNA index and proliferative index were well correlated with the histologic grade.

Proliferative Activity of Thyroid Lesions Evaluated by Mitotic Count and Proliferating Cell Nuclear Antigen (PCNA).: Hwa Sook Jeong, Geon Kook Lee, Hyung Geun Song, Ro hyun Sung; Korean J Pathol. 1997;31(12):1297-1307.

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Abstract PDF: To evaluate the clinical and histopathological significance of the proliferative activity in neoplastic and non-neoplastic thyroid lesions, we analyzed the mitotic count and the proliferating cell nuclear antigen labeling index (PCNA-LI) by immunohistochemistry as the proliferation- related markers. In this study included were surgically removed normal thyroid tissue (27 cases), adenomatous goiter (15 cases), Hashimoto's thyroiditis (5 cases), follicular adenoma (13 cases), follicular carcinoma (7 cases), papillary carcinoma (44 cases), poorly differentiated carcinoma (2 cases) and undifferentiated carcinoma (3 cases). The median PCNA-LI was 0 in normal thyroid tissue, 0.5 in adenomatous goiter, 6.2 in Hashimoto's thyroiditis, 1.2 in follicular adenoma, 4.8 in follicular carcinoma, 8.5 in papillary carcinoma, 60.8 in poorly differentiated carcinoma, and 55.2 in undifferentiated carcinoma (p=0.0001). Although PCNA-LI was exceptionally high in Hashimoto's thyroiditis, it was suggested that PCNA-LI could be used as a marker differentiating benign lesions from malignant neoplasm. Also, it could differentiate follicular adenoma from follicular carcinoma. Except clinical stage (p=0.0397), PCNA-LI was not related with sex, size, histologic subtype, and lymph node metastasis in papillary carcinoma. The presence of mitosis differentiated the neoplastic thyroid lesions from the non-neoplastic lesions (p<0.05), however, it could not divide benign and malignant neoplasm. These results suggest that an evaluation of the proliferative activity can help to differentiate the thyroid lesions. In addition, there was no significant correlation between the value of PCNA-LI and the presence of mitosis. It can be recommended to evaluate both the mitotic count and the PCNA-LI for determining the proliferative activity of the thyroid lesions.

Clinicopathological Analysis of Laryngeal Leukoplakia: Clinical Follow-up and Immunohistochemical Expression of p53 and PCNA.: Yang Soon Park, Sang Yoon Park, Soon Ae Oak, Gyung Yup Gong, Joo Ryung Huh, Eun Sil Yu, In Chul Lee, Ghee Young Choe; Korean J Pathol. 1996;30(4):318-327.

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Abstract PDF: Laryngeal leukoplakia is seen in a number of pathologic settings such as keratosis without atypia(KWOA), keratosis with atypia(KWA), squamous cell carcinoma in situ(CIS) and invasive squamous cell carcinoma, and it continues to be a confusing and controversial topic for both otolaryngologist and pathologist. This is largely due to the use of ambiguous and inconsistent terminology, the lack of unanimous agreement on the definition of these terms, failure of the clinician to obtain a representative biopsy, and the subjectivity of the pathologist interpreting the biopsy. To evaluate the applicability of the expression pattern of p53 and PCNA in borderline cases of histopathologic classification, we performed a histopathologic analysis of leukoplakia to includ clinical follow-up, correlation of disease progression and degree of atypia, and expression of p53 and PCNA according to the degree of atypia. Histologically, laryngeal leukoplakia included seven cases of KWOA, fourteen cases of KWA (mild-2, moderate-8, severe-4), three cases of CIS, and one case of invasive squamous cell carcinoma. Keratosis with atypia, a moderate degree or more, showed a strong tendency to progress to invasive carcinoma(p<0.05). The degree of p53 and PCNA expression correlated with the degree of atypia(p<0.05). p53-positive cases at the initial biopsy clearly tended to recur and develop into invasive carcinoma(p<0.01).

Detection of bcl-2/IgH Gene Rearrangement and Expression of c-myc and p53 Oncoprotein in B-cell Lymphoma.: Ghee Young Kwon, Chul Woo Kim; Korean J Pathol. 1996;30(5):437-446.

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Abstract PDF: Many kinds of genetic changes have been known to be associated with malignant lymphoma and bcl-2, p53 and c-myc are some examples. We investigated the expression of p53 and c-myc protein in follicular and diffuse B cell lymphoma by immunohistochemistry to study the possible role of these proteins in the lymphomagenesis and transformation of the tumor. The rearrangement of bcl-2 oncogene and the immunoglobulin heavy chain gene was searched for in those cases by polymerase chain reaction(PCR). Paraffin-embedded tissues of fifteen follicular lymphomas and 14 diffuse lymphoma cases were used. The results of immunohistochemical staining are summarized as follows: 1) p53 positivity is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.001); 2) c-myc expression is not increased in diffuse lymphoma compared with follicular lymphoma; 3) PCNA index is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.03) but there was no statistically significant correlation between PCNA index and p53 positivity(P=0.44); 4) Eight out of 14 cases of follicular lymphoma and 12 of 14 cases of diffuse lymphoma showed rearrangement of the immunogloblulin heavy chain gene; 5) bcl-2 oncogene rearrangement was identified in only one case of follicular lymphoma and all the diffuse type lymphomas were negative in bcl-2/IgH rearrangement. In conclusion, assuming that the follicular pattern of B-cell lymphoma often transforms to diffuse type in later stages, c-myc over-expression might be an earlier event than p53 mutation in the process of tumor progression in B-cell lymphoma. bcl-2/IgH gene rearrangement in follicular lymphoma is a rare finding in Korea compared to that of Western countries.

Expression of Proliferating Cell Nuclear Antigen and p53 Protein in Ovarian Epithelial Tumors.: Jong Jae Jung, Jong Hee Nahm, Chang Soo Park; Korean J Pathol. 1998;32(3):193-200.

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Abstract PDF: p53 gene mutation is commonly accepted to be associated with loss of negative cell cycle control and progression of tumors. The proliferative activity of tumor cells is considered to be a valuable indicator of tumor aggressiveness. This study is intended to compare p53 protein expression with cell proliferation rates in the ovarian epithelial tumors according to the various clinicopathological parameters. Immunohistochemistry using monoclonal p53 antibody (DO-1) and PCNA antibody (PC10) was applied to 56 cases of ovarian epithelial tumors including 17 cases of borderline tumor. The results were as follows. Both immunohistochemical staining of PCNA and p53 protein showed positive reactions confined to the nuclei of tumor cells. There were significant differences of p53 protein expression rates between borderline malignancies (11.8%) and cystadenocarcinomas (56.4%) of ovary. The expression rate of p53 protein was not significantly different according to the differentiation and the stage, but the cases of strong positive reaction to p53 protein were more frequently noted in the poorly differentiated and advanced staged tumors. The PCNA indices of p53 strong positive cases were higher than those of p53 weak positive cases. In summary, p53 protein and PCNA expression may be used as an adjuvant in differentiating borderline lesions from carcinomas of ovary and predicting their biological behaviors.

Evaluation of Prognostic Significance of AgNORs and PCNA during 9,10-dimethyl-1,2-benzantracene(DMBA)-induced Hamster Buccal Pouch Carcinogenesis.: Sam Pyo Hong, Myong Soon Song, Seong Doo Hong, Jae Il Lee, Chang Yun Lim; Korean J Pathol. 1998;32(5):337-345.

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Abstract: The purpose of this study is to evaluate the prognostic significance of argyrophilic nucleoalr organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) by using DMBA hamster buccal pouch carcinogenesis which provides a good experimental model in reproducing steps from precancerous lesions to invasive squamous cell carcinomas. The buccal pouches of 50 Syrian hamsters were applied with 0.5% DMBA in mineral oil three times a week to reproduce various lesions from precancerous ones such as hyperkeratosis or epithelial dysplasia to invasive squamous cell carcinomas. Their sections were stained with H & E, and silver colloid, and processed immunohistochemically by being applied with monoclonal antibody to PCNA. The histopathologic examainations were done and the counts of AgNORs were evaluated. The PCNA labelling indices on each lesions were evaluated. The correlation between histopathological grades and counts of AgNORs or PCNA labelling indices were evaluated. The number of AgNORs was 2.22+/-0.22 in control group, 3.46+/-0.72 in carcinoma in situ (CIS), 3.78+/-0.63 in squamous cell carcinoma (SCC), respectively. AgNORs significantly increased in severe epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The PCNA Labeling Index (LI) was 39.47+/-6.68% in control group, 79.61+/-4.14% in CIS, and 85.43+/-6.25% in SCC, respectively. PCNA LI also significantly increased in epithelial dysplasia, CIS, and SCC compared with normal tissue (P<0.05). The number of AgNORs, AgNOR area, and PCNA LI slightly increased in the advancing front than in the center of SCC, but, it was not statistically significant. It appeared that there were a good correlation between the number of AgNORs and PCNA LI (Pierson correlation coefficient : 0.649, P<0.001). These results suggested that the number of AgNORs and the PCNA LI could be useful markers for evaluating the risk of malignant transformation and prognosis of SCC. It was thought that the clinical usefulness of these markers should be verified by using human tissue specimens.

PCNA Labelling index and AgNORs of Transitional Cell Carcinoma of the Urinary Bladder.: Byung Gon Park, Sang Yong Lee, Mee Sook Roh, Seo Hee Rha, Sook Hee Hong; Korean J Pathol. 1994;28(5):469-477.

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Abstract PDF: Proliferating cell nuclear antigen (PCNA, PC10), an auxillary protein of DNA polymerase, plays a main role in the early stage of DNA Synthesis and is synthesized from Gl phase to s phase of the cell cycle. Nucleolar organizer region (NORs) are DNA loops encoding RNA proteins(AgNORs). To evaluate correlation with PCNA labelling index (LI)and AgNORs according to histological grades and clinical stages of transitional cell carcinoma of the urinary bladder, the authors analysed 54 transitional cell carcinoma using immunohistochemical stain for PCNA and silver stain for AgNORs in paraffin sections. The comparison of PCNA (PC10) LI and clinical stage showed a significant correlation (p<0.05), where as PCNA (PC10) LI according to histologic grade showed no significant correlation. High grade tumors showed increase PCNA LI. Superficial tumors (Ta-Tl) showed significantly lower PCNA LI than muscle invasive tumors (T2-T4)(p<0.05). There was no significant correlation between AgNORs and clinical stage, bur higher stage and higher grade tumors showed increased noubers of AgNORs. These results suggest that PCNA LI has a significant correlation with clinical stages of transitional cell carcinoma of the urinary bladder.

Castration-induced Apoptosis in the Rat Prostate.: Ki Kwon Kim, Sang Sook Lee; Korean J Pathol. 1998;32(6):431-442.

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Abstract: This study was carried out to investigate the morphologic findings and process of castration-induced apoptosis in the rat prostate. The experimental group was treated with bilateral orchiectomy followed by sequential sacrifices at 1, 2, 3, 4, 5, 6, 7 days and 2, 3 weeks (6 rats, respectively). Ventral prostate was extirpated and examined by light microscopic and immunohistochemical, ultrastructural observation. Apoptotic index increased by 4 days after castration and decreased thereafter. ApopTag stain revealed brownish granular pattern in the nucleus of apoptotic cells. DNA fragmentation rate was 0.5% in the control group and began to increase by 1 day after castration and reached to 11.1% by 4 days and decreased thereafter. PCNA stain showed brownish granular pattern in the nucleus of some epithelial cells of the prostatic glands. PCNA labelling index was 2.4% in the control group and reached peak by 3 days after castration and decreased thereafter. Electron microscopically, there was chromatin condensation with margination toward the nuclear membrane by 1 day after castration. Also noted were condensation of cytoplasm, dilatation of RER and nuclear fragmentation. Apoptotic bodies were formed and phagocytosed by adjacent cells and some apoptotic bodies were found in the lumen of acini. Based on these results, it can be concluded that castration-induced prostatic involution is the result of apoptosis. Detection of DNA fragmentation with ApopTag is a more a accurate method to identify not only apoptotic body formation itself but also the previous step of apoptotic body formation. PCNA labelling index to identify the cellular proliferation seems to play an active role in the early step of apoptosis and be a good tool for investigation of apoptosis.

Prognostic Significance of PCNA Index and AgNORs Score in Transitional Cell Carcinoma of the Renal Pelvis.: Wan Seop Kim, Seung Sam Paik, Nam Hoon Kim, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(7):521-530.

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Abstract: Proliferative activity of a malignant tumor is known to reflect its biological aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells. In transitional cell carcinoma of the renal pelvis, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNORs count in 22 transitional cell carcinoma of the renal pelvis to assess their prognostic significance compared with their cumulative survival rate, the stage of disease and histopathologic features of the tumors. An immunohistochemical method and a standard colloidal silver staining were used. The mean percentage of PCNA positivity (PCNA index) and the mean number of AgNORs per nucleus (AgNORs score) were determined. In a multivariable analysis, PCNA indexes were significantly associated with tumor stage (p=0.024), whereas AgNORs scores were not significantly associated with the stage or histopatholgic features of the tumors. Histologic grade was correlated to disease stage at a significant level (p=0.000). But there was a trend of low tumor PCNA-indices or AgNORs counts with survival advantage for patients, but this did not reach statistical significance. The results suggest that the fraction of PCNA positive nuclei would be useful for investigating the malignant potential of renal pelvic cancers, although their clinical use as markers of biologic behavior may be limited.

Classification of Gastrointestinal B-cell Lymphoma and Expression of Cyclin D1, bcl-2, bcl-6, p53 Protein and PCNA.: Ji Han Jung, An Hee Lee, Chang Suk Kang, Byung Kee Kim; Korean J Pathol. 2000;34(6):437-445.

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Abstract PDF: Until recently, the gastrointestinal lymphomas were classified according to the criteria developed for the node-based lymphomas. In recent years, the REAL classification provided a new category of MALT lymphoma and Mantle cell lymphoma in B-cell lymphomas. Low-grade MALT lymphomas have been well characterized clinically, histologically, and immunophenotypically. We retrospectively recategorized 41 cases of the primary gastrointestinal B-cell lymphoma and investigated the expression of cyclin D1, bcl-2, bcl-6, p53 protein, and PCNA by immunohistochemical method. The cases were categorized in 5 groups, low grade MALToma, low/high grade MALToma, high grade MALToma, diffuse large cell lymphoma, and mantle cell lymphoma according to the morphological findings. The expression of cyclin D1 protein was restricted to the cases of mantle cell lymphoma. The bcl-2 protein expression was higher in the low grade MALT lymphoma than in the high grade lymphoma (P=0.006). The bcl-2 protein expression was higher in the low grade area than in the high grade area in the low/high grade MALT lymphoma (P=0.005). The bcl-6 and p53 protein expression was higher in the high grade MALT lymphoma than in the low grade lymphoma (P=0.022, P<0.018). However, the bcl-6 protein expression of the tumor cells was higher in high grade area than in low grade area in the low/high grade MALT lymphoma (P=0.004). The degree of the PCNA expression was positively correlated with the grade of the malignant lymphoma (P=0.003). The above results suggest that the cellular proliferation assessed by PCNA index correlates with the histologic grade. And the bcl-2, bcl-6, p53 protein may be effective in the transition from the low grade MALT lymphoma to the high grade lymphoma. Therefore, we can differentiate the low grade lymphoma from the high grade lymphoma by the immunohistochemical staining for cyclin D1, bcl-2, bcl-6, p53 protein and can predict the prognosis of the patients in accordance with the grade of the tumor.

Expression of Met Protein in Colorectal Carcinoma.: Kyung Un Choi, Jin Sook Lee, Chang Hun Lee, Mee Young Sol, Kang Suk Suh; Korean J Pathol. 2000;34(7):501-508.

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Abstract PDF: Met protein is a transmembrane 190 kD heterodimer with tyrosine kinase activity, encoded by c-Met oncogene. It serves as a high affinity receptor for hepatocyte growth factor (HGF)/scatter factor (SF), a cytokine which stimulates cell proliferation, motility, and invasion. In this study, we immunohistochemically evaluated the expression of Met/hepatocyte growth factor receptor in colorectal cancers. Met protein was expressed in 31 of 72 patients (43.1%). The staining pattern was cytoplasmic in nature, present throughout the tumor, and showed variable intensity from case to case. The relationship between the expression rate and intensity, and age and sex of patients, tumor size (p=0.645), tumor site (p=0.902) and tumor differentiation (p=0.844) was not statistically significant. The expression rate and intensity were significantly correlated with lymphovascular invasion (p=0.001), lymph node metastasis (p=0.010), depth of invasion (0.019), and stage (p=0.023). Cytoplasmic accumulation of Met protein was not associated with enhanced PCNA index of tumor cells (p=0.052). These results suggest that Met protein may play an important role in the invasion and metastasis of colorectal cancer cells.

Liver Cell Dysplasia: Analysis of 141 cases with reference to histopathologic Characterization and proliferative activity.: Sang Yong Song, Yong Il Kim; Korean J Pathol. 1992;26(4):338-347.

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Abstract PDF: Liver cell dysplasia of Anthony(LCD) is a common association in hepatocellular carcinoma(HCC)-bearing liver and has been regarded as a premalignant condition with strong linkage to hepatitis B virus infection and cirrhosis. A total of 189 surgically resected livers [HCC(168 cases), cholangiocarcinoma(3 cases), metastatic carcinoma(3 cases), and non-neoplastic lesions(15 cases)] were reviewed to elucidate the nature of LCD by means of light microscopic examination, in situ hybridization method for HBV DNA and expression of proliferatin cell nuclear antigen(PCNA) using immunohistochemical technique. LCD was present in 141 cases(74.6%), and its prevalence rate was independently significant in HCCs with or without cirrhosis than other groups. There was no difference in mean age, although LCD-positive group was younger than its negative counterpart. Association rate of LCD in HCC-cirrhosis group was statistically significant than the non-cirrhotic group, and higher histological grading of LCD was correlated well with wider distribution pattern and clustering. Seropositivity of HBsAg was not correlated with presence of LCD or with histological grading. In situ hybridization techique using HBV DNA probe demonstrated fine granular stainable particles even in LCD cells. Immunohistochemical study for PCNA revealed that the proliferative activity of LCD was lower than that of the cirrhotic cell. With the above results it is concluded that LCD reflects neither a regenerating condition nor a premalignant lesion but suggest a reactive change.

The prognostic significance of tumor angiogenesis, proliferating cell nuclear antigen(PCNA), and the Ki-67 index in carcinoma of the uterine cervix.: Chan Pil Park, Seung Yon Lee, Moon Hyang Park; Korean J Pathol. 1997;31(1):1-14.

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Abstract PDF: Angiogenesis, the induction of new capillaries and venules, is associated with tumor growth. This study was designed to determine whether cervical carcinomas are angiogenic, and to investigate whether tumor angiogenesis can serve as a prognostic factor in cervical carcinoma. Surgical specimens of 47 cervical carcinomas were immunohistochemically stained specifically for endothelial cells with factor VIII-related antigen to identify all vessels. Microvessels were counted from photographs of 200x microscopic fields. In addition, thirty-seven cases were studied by immunohistochemical means using the monoclonal antibodies for PCNA and for Ki-67 to determine tumor cell proliferation rates in cervical carcinomas. The microvessel count(MVC), the PCNA labelling index, and the Ki-67 index were calculated and compared with known prognostic factors and disease free survival rates in cervical carcinomas. A wide range in the MVC count(range 12-100 mean=38.2+/-19.2), the PCNA labeling index(8-69% mean=33.6+/-15.2%), and in the extent of Ki-67 staining(0-43% mean=10.3+/-10.5%) was observed, indicating considerable variation of tumor angiogenic activity and tumor growth rates. This study showed statistically significant correlations in disease free survival rates with both lymph node status and the microvessel count. However, there was no significant difference in disease free survival rates between tumor stage, age, the PCNA labelling index, and the Ki-67 index.

A Study of the Correlation between Cellular Proliferating Activities and Prognosis in Gastrointestinal Stromal Tumors .: Hee Jin Chang, Duck Hwan Kim, Sung Sook Pang, Jin Hee Sohn, Jung Il Suh, In Sun Kim, Jong Sang Choi; Korean J Pathol. 1995;29(2):152-169.

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Abstract PDF: Gastrointestinal stromal tumors are notorious for their unpredictable clinical behavior. To assess the cellular proliferating activities, four different methods were used: mitotic count, nucleolar organizer region(AgNOR) staining, immunostaining of proliferating cell nuclear antigen (PCNA) and DNA ploidy were used on 39 cases of gastrointestinal stromal tumors. Additionally, we analysed cellularity, cellular atypism and necrosis. Among 39 cases of gastrointestinal stromal tumors, 11 cases were diagnosed as benign lesions according to clinicopathologic findings. Malignant lesions were arbitrarily classified into low grade(n=ll) and high grade(n=17) on the basis of absence or presence of recurrence, metastasis or tumor-related death during the follow-up period. Numbers of mitosis, AgNORs, PCNA index and DNA ploidy were correlated with grades of tumor and prognosis. Among them, AgNORs counting appeared to be the most useful in predicting prognosis. Numbers of mitosis, PCNA index and DNA ploidy showed varying degrees of overlap among the 3 groups. Among the histological parameters, cellular atypia showed some relationship with the prognosis that others did not reveal.

The Relationship of Ki-67, Proliferating Cell Nuclear Antigen, AgNORs and p53 Protein Expression in Astrocytoma.: Dong Ja Kim, Jae Weon Lim, Yoon Kyung Sohn; Korean J Pathol. 1999;33(1):25-31.

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Abstract PDF: The grading of astrocytoma has traditionally relied on histological assessment, but there are some differences in their parameters, application, and reproducibility. Recently, numerous studies have attempted to correlate biological aggresiveness with tumor proliferation index using new immunohistochemical methods. The purpose of this study is to correlate the histopathological grades of astrocytoma with the expression of Ki-67, PCNA, p53 protein and AgNORs. The paraffin sections of 41 consecutive cases of astrocytomas were examined. Histologically the tumors were graded as three groups under the St. Anne-Mayo system and showed 14 cases in grade II, 15 cases in grade III and 12 cases in grade IV (glioblastoma multiforme). As a result, the Ki-67 labelling index and p53 protein expression tended to increase with increasing grade of malignancy. But the univariate analysis showed that there was no significant difference between the tumor grades (p>0.05). The PCNA labelling index and number of AgNORs revealed striking differences between the grade II and grade III astrocytomas (p<0.05). We concluded that the PCNA labelling index and AgNORs counting are useful markers for differentiation between grade II and III astrocytomas.

A Study on Immunohistochemical Stain for S-100 Protein, HMB 45 and Proliferating Cell Nuclear Antigen(PCNA) of Spitz Nevus Compared with Benign Nevus and Malignant Melanoma.: Mee Yon Cho, Kwang Gil Lee, Myung Wook Kim; Korean J Pathol. 1992;26(6):552-560.

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Abstract PDF: The differential diagnosis between Spitz nevus and malignant melanoma is difficult due to similar histologic findings. To obtain the useful aids for the differential diagnosis between two diseases, we studied 13 cases of Spitz nevus, 8 benign nevi of compound and intradermal, and 9 melanomas of primary and metastatic, using the immunohistochemical stain for S-100 protein, HMB.45 and proliferating cell nuclear antigen(PCNA). The staining pattern and intensity of S-100 protein showed homogenously strong positive reactivity in all cases. The frequency of HMB.45 positive cell in Spitz nevus was significantly lower than that in melanoma. When compared with the usual compound and intradermal nevi, Spitz nevi showed more significantly positive reaction in the dermal component of nevus cells. The expression of PCNA was higher in melanoma than in Spitz nevus. The immunohistochemical stains for HMB.45 and PCNA are considered as a useful methods for differentiation between Spitz nevus and melanoma, while stain for S-100 protein is not helpful.

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