Journal of Pathology and Translational Medicine

Original Articles

Expression Patterns of Bcl-2 and PCNA in Cervical Intraepithelial Neoplasia.: Mee Sook Roh, Gi Yeung Huh, Sook Hee Hong; Korean J Pathol. 1995;29(6):703-713.

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Abstract PDF: Immunohistochemical stains for bcl-2 oncoprotein and PCNA and examination of the mitosis level were perfon-ned in 76 cases of cervical intraepithelial neoplasia (CIN). We studied the expression pattern of bcl-2 protein according to histologic grades and the function of bcl-2 oncogene associated with cellular proliferation by comparing with PCNA expression and the mitosis level. The results were as follows: 1) Of 76 cervical intraepithelial neoplasias, 23 (30.3%) were CIN I, 23 (30.3%) were CIN II, and 30 (39.4%) were CIN III. 2) Of 23 CIN I cases, grade 0 and 1 mitosis level were seen in 20 (87.0%), PCNA in 16 (69.6%), and bcl-2 in 19 (82.6%) cases, respectively, which indicates that CIN I lesions have a low cellular proliferative activity. 3) Of 30 CIN III cases, grade 2 and 3 mitosis level were noted in 28 (93.3%), PCNA in 25 (83.3%) and bcl-2 in 19 (63.3%) cases, respectively, which indicates that CIN III lesions have a high cellular proliferative activity. The results suggest that progressive increase of dysfunctional proliferative activity and abnormal decrease of cell death result in increased number of neoplastic cells according to CIN grade. Also the expression rate of bcl-2, PCNA and mitosis level were significantly different between CIN I and 111, which suggest that they might be good parameters for classifying CIN into low and high grade and for prediction of the biologic behavior of the CIN lesion.

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 Transforming Growth Factor-beta and Procollagen III with Regenerative Activity in Acute Liver Injury, and the Effect of Prostaglandin E2.: Nam Hoon Cho, Chan Il Park; Korean J Pathol. 1996;30(5):367-387.

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Abstract PDF: Transforming growth factor-beta (TGF-beta) plays an important role in hepatic fibrogenesis. It is thought to inhibit regeneration of the hepatocytes. The aim of this present study was to clarify the correlation of TGF-beta, collagen type III (PIIINP) and the regenerating activity of hepatocytes, and the effect of prostaglandin E2 (PgE2) on them in acute liver injury. Two hundred and sixteen male Sprague-Dawley rats, weighing 200g on average, were divided into six experimental groups and two control groups; group I-CCl4 only administration, group II-partial hepatectomy(PH) only, group III-PH following CCl4 administration, group IV-olive oil only administration, group V-sham operation, group VI-CCl4 administration with pretreatment of PgE2, group VII- PH with pretreatment of PgE2, and group VIII- PH following CCl4 administration with pretreatment of PgE2. Five rats were sacrificed at 12, 24, 36, 48, 96 and 168 hours after the administration of CCl4 or PH in each experimental group. The liver was tested with immunohistochemical stain for proliferating cell nuclear antigen (PCNA) and in situ hybridization for TGF-beta. Radioimmunoassay for serum PIIINP was also performed. The results were as follows: TGF-beta was expressed mainly in the perisinusoidal cells and periportal mesenchymal cells. The TGF-beta positive cells were most numerous in the combined group of CCl4 plus PH. TGF-beta expression tended to have an inverse relation, with the PCNA index in all experimental groups. The PCNA index was highest in the CCl4 only group and lowest in the combined group of CCl4 plus PH. The PH only group showed a peak PCNA index at 48 hours. In the CCl4 only group and the combined group of CCl4 plus PH, serum PIIINP appeared to increase at 12 hours or more after the expression of hepatic TGF-beta. Pretreatment of PgE2 revealed that TGF-beta precipitously disappeared at 48-96 hours after insult. PgE2 influenced the vanishing period, not the emerging time of TGF-beta and had a remarkable effect on the amount of TGF-beta especially in the PH following CCl4 administration group, which resulted in significant accentuation of PCNA indices. In conclusion, PH of the prior injured liver induces a marked increase of TGF-beta followed by a significant suppression of regeneration of the remaining liver, and PgE2 overtly suppresses the expression of TGF-beta.

Expression of Insulin-like Growth Factor-I-Receptor in Colorectal Adenomas and Carcinomas.: Young Chae Chu, Hye Seung Han, Jee Young Han, Joon Mee Kim, Young Bae Kim, Tae Sook Hwang; Korean J Pathol. 2000;34(3):199-207.

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Abstract PDF: The activation of the insulin-like growth factor-I-receptor system (IGF-IR) has recently emerged as critical events in transformation and tumorigenicity of several human tumors. In this study we investigated the expression of IGF-IR in 33 colorectal adenomas, 88 primary colorectal carcinomas, and 30 normal colonic mucosa adjacent to the carcinoma. Immunohistochemical staining (IHC) for IGF-IR was performed on paraffin embedded sections using an anti-IGF-IR rabbit polyclonal antibody. IHC stains for IGF-IR were scored using a semiquantitative scoring system. The relationship of IGF-IR staining to clinicopathologic variables and proliferating cell nuclear antigen (PCNA) staining was also analysed. The mean IHC scores for IGF-IR of normal glands, adenoma, intramucosal carcinoma, node-negative carcinoma, and node-positive carcinoma were 0.41 0.96, 0.76 1.23, 2.0 1.48, 2.83 2.0 and 5.93 1.58, respectively. These scores for each category were statistically significant except between normal glands and adenoma and between intramucosal carcinoma and node-negative carcinomas. The mean PCNA indexes of normal glands, adenoma, intramucosal carcinoma, node-negative carcinoma, and node-positive carcinoma were 2.48 2.60, 6.94 11.03, 27.21 11.42, 43.36 9.9 and 57.60 10.01, respectively. The PCNA index for each category was statistically significant except between normal and adenoma. IGF-IR scores and PCNA indexes were higher with tumor progression and also correlated each other (sr=0.65, p=0.0001). Higher IGF-IR scores and PCNA indexes were seen in tumors with advanced stage, infiltrative growth pattern, poor differentiation, nerve invasion, lymphovascular invasion, and moderate fibrosis. Our results suggest that IGF-IR plays an important role in tumorigenicity and tumor progression.

A Study on the Expression of Proliferating Cell Nuclear Antigen and Apoptosis of the Hepatocellular Carcinoma in Human and Hepatitis B Virus X Transgenic Mice.: Hyung Bae Moon, Dae Yeul Yu, Hyung Ryun Yoo, Byung Joon So, Kwon Mook Chae, Haak Cheol Kim, Ki Jung Yun, Won Cheol Han, Hyang Jeong Jo, Bo Yong Kim; Korean J Pathol. 2001;35(2):129-136.

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Abstract PDF: BACKGROUND
This experiment was designed to study the cell kinetics of hepatocellular carcinoma (HCC) in both hepatitis B virus X (HBx) transgenic mice and humans.
METHODS
The immunohistochemical stain of proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay of apoptosis were used on formalin fixed-paraffin embedded tissues.
RESULTS
PCNA labeling indices (PCNA-LI) in the liver of HBx transgenic mice were markedly increased in HCC (11.3%) compare to the dysplastic areas (1.3%) and in the liver of non-transgenic littermates (0.1%). There was no significant difference of PCNA-LI in the dysplastic areas between HCC developed mice and non-HCC developed mice. Apoptosis labeling indices (Apoptosis-LI) in both the dysplastic areas and HCC of HBx transgenic mice were similar to those of non-transgenic littermates. PCNA-LI was markedly increased in human HCC (28.9%) compare to the background of HCC (2.9%) and the control liver (2.9%). Apoptosis-LI was decreased in human HCC (0.3%) compare to the background of HCC (0.4%) and the control liver (1.0%). Conclusion : There is a marked increase of cell proliferating activity in human HCC and in HCC of HBx transgenic mice, and there is a decrease of apoptosis in human HCC, but not in HCC of HBx transgenic mice.

Apoptosis in Renal Hypertrophy after Uninephrectomy in the Rats.: Chan Pil Park, Jung Woo Noh, Joo Seob keum, Myung Sook Kim, Moon Hyang Park; Korean J Pathol. 2001;35(6):513-523.

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Abstract: BACKGROUND
Glomerular compensatory hypertrophy maintains decreased renal function after uninephrectomy (UNX). Proliferation and apoptosis of renal cells may be involved in hypertrophy.
METHODS
In small and large male Sprague-Dawley rats, contralateral kidneys were harvested 1, 7, 14 and 30 days after UNX. Apoptosis was assessed by the Tdt-mediated dUTP-digoxigenin nick end labelling method. Proliferating cell nuclear antigen and Fas ligand (FasL) expression was determined by immunohistochemically.
RESULTS
Morphometrically, glomerular hypertrophy was observed in both small and large rats after UNX, and it was more significant in the small rats. The glomerular proliferation index (PI) was gradually increased from day 7 but decreased on day 30 in the small rats. Glomerular PI was significantly increased from day 7 in large rats and peaked at day 14. Apoptotic cells in the glomeruli were slightly increased on day 1 and on day 7 in both groups of rats. The expression of FasL was gradually increased in the distal tubular epithelium in both groups.
CONCLUSIONS
These results demonstrate different profiles regarding the compensatory growth of the kidney, cell proliferation, and apoptosis during the period of compensatory hypertrophy in uninephrectomized rats of different weight and age. Apoptosis may play a role in regressing a number of proliferated cells during renal compensatory hypertrophy.

Expression of Proliferating Cell Nuclear Antigen (PCNA) of Major Intrahepatic Bile Duct Epithelium in Resected Liver Tissue with Hepatolithiasis and Hepatolithiasis Associated with Cholangiocarcinoma.: Shi Nae Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2002;36(4):232-237.

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Abstract PDF: BACKGROUND
Histologic progressive changes of bile duct epithelium with hyperplasia, dysplasia and cholangiocarcinoma could be caused by hepatolithiasis. To be clarified as a neoplastic process, this histologic process should be evaluated with various aspects of cell biology.
METHODS
Immunohistochemical study of proliferating cell nuclear antigen (PCNA) was performed on 45 cases (10; normal, 15; hyperplasia, 14; low-grade dysplasia:LGD, 6; high-grade dysplasia: HGD) of hepatolithiasis and 10 cases (all HGD) of hepatolithiasis with cholangiocarcinoma.
RESULTS
In the hepatolithiasis, mean PCNA labelling indices (LI) of normal, hyperplasia, LGD and HGD of major intrahepatic bile duct epithelium were 24.5+/-4.3, 51.5+/-0.1, 62.0+/-.4 and 84.7+/-.3, respectively and gradually increased. Mean LI of PCNA in HGD of major intrahepatic bile duct epithelium of hepatolithiasis with cholangiocarcinoma was 68.7+/-.7, which was similar to that of LGD in hepatolithiasis without cholangiocarcinoma.
CONCLUSIONS
Histologic transformation through hyperplasia, dysplasia and carcinoma in major intrahepatic bile duct epithelium of hepatolithiasis may be a neoplastic process if these histologic changes are evaluated in the cellular proliferation aspect.

Effect of Antenatal Dexamethasone Treatment on Neuronal Morphogenesis.: Soo Jeong Yoon, Heasoo Koo, Chong Il Kim; Korean J Pathol. 2005;39(2):81-90.

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Abstract PDF: BACKGROUND
Glucocorticoids (GCs) are essential for normal development and the maturation of the central nervous system. The aim of this study was to determine the effects of antenatal dexamethasone (DEXA) treatment on neuronal morphogenesis and on the glial cell line-derived neurotrophic factor (GDNF) protein expression in neonatal rat.
METHODS
Pregnant Sprague-Dawley rats were injected with saline (the control), or 0.2 mg/kg/day DEXA or 0.8 mg/kg/day DEXA at 17th, 18th and 19th day of gestation. The newborn rat brains were examined at postnatal days 1 (n=75) and 10 (n=78).
RESULTS
The DEXA-treated groups showed distorted architectures of neurons in the cerebral cortex, hippocampus and cerebellar cortex at postnatal days 1 and 10 with an increased number of proliferating cell nuclear antigen (PCNA)-positive cells. The cerebellar cortex in the DEXA-treated groups showed delayed development with more PCNA-positive cells in the internal granular cell layer. The Purkinje cells showed a markedly decreased number and the decreased length of the dendritic processes. The GDNF positive reaction was decreased in the DEXA-treated groups in a dose-dependent manner.
CONCLUSIONS
The developmental changes and neuronal degeneration at postnatal days 1 and 10 in the newborn rats that were exposed to DEXA at the late gestational age were associated with increased proliferative activity and a decreased level of GDNF protein expression.

Clinicopathologic Significance of CD44s, CD44v5 and CD44v6 Expression in Non Small Cell Lung Carcinomas.: Jae Kyun Kim, Chang Hun Lee, Kyeong Min Lee, Jin Mi Song; Korean J Pathol. 2004;38(2):93-99.

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Abstract PDF: BACKGROUND
CD44 is a polymorphic family of transmembrane glycoproteins generated by alternative splicing of messenger RNA and is involved in the mechanism of tumor invasion and metastasis.
METHODS
The expression of selected CD44 molecules (CD44s, CD44v5, and CD44v6) was determined immunohistochemically in 84 cases of non small cell lung carcinomas (NSCLCs). The results were compared with PCNA index, microvessel density (MVD), and clinicopathological parameters including patient? survival.
RESULTS
CD44s showed a positive reaction in 61.9% (52/84) of NSCLCs, CD44v5 in 73.8% (62/84), and CD44v6 in 39.3% (33/84). Squamous cell carcinomas (SCCs) displayed preferential expression of all CD44 molecules in comparison with adenocarcinomas (ACs) (p<0.001). As a whole, the expression of CD44 molecules was not correlated with clinical parameters (stage, TNM-T, and TNM-N), PCNA index, or MVD. For ACs only, however, CD44v5 expression was negatively correlated with PCNA index (p<0.05). Poor survival was correlated with CD44v5 expression in ACs and CD44v6 in SCCs (both, p<0.05).
CONCLUSIONS
These findings suggest that CD44 molecule in NSCLC could be a distinctive phenotypic marker for SCC, and the possibility that CD44v5 and CD44v6 are in some way instrumental in conditioning the biologic behavior of NSCLC according to major histologic types.

Prognostic Significance of P53, BCL-2 and PCNA in Diffuse Large B-Cell Lymphoma: Correlation with International Prognostic Index.: Dong chul Kim, Gyeongsin Park, Ahwon Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang; Korean J Pathol. 2003;37(6):407-412.

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) represents a diverse spectrum of clinical presentation, morphology, and genetic and molecular alterations, and shows variable prognoses and responses to therapy. The International Prognosis Index (IPI) is widely used to predict prognosis but is not precise.
METHODS
Thirty-nine cases of DLBCL were classified into low- and high-risk groups according to IPI and were analyzed for their p53, BCL-2, BCL-6 and PCNA expression profile by immunohistochemical staining and overall survival rate.
RESULTS
The mean age of the 39 patients, 23 males and 16 females, was 52.6 years. There were 23 cases (59.0%) in the low-risk group and 16 (41.0%) in the high-risk group. p53, BCL-2, BCL-6 and PCNA expression was higher in the high-risk group than in the low-risk group, but only the differences in p53 and BCL-2 expression were statistically significant (p < 0.05).
CONCLUSION
The p53 and BCL-2 protein expression in DLBCL may supplement IPI in predicting the prognosis of DLBCL patients.

Immunohistochemical Study on the Proliferative Activity of Human Thyroid Tumors.: Myoung Jae Kang, Young Jin Jeong, Woo Sung Moon, Myoung Ja Jeong, Joo Heon Kim, Dong Geun Lee, Ho Yeul Choi, Sang Ho Kim; Korean J Pathol. 1995;29(1):77-84.

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Abstract PDF: For the estimation of the proliferative activity, related to the biologic behaviour, malignant potential, and prognosis, of human thyroid tumors, PCNA(proliferating cell nuclear antigen) immunohistochemical staining was performed on paraffin-embedded sections of 9 normal thyroid tissues, 9 adenomatous goiters, 9 follicular adenomas, 4 Hurthle cell tumors, 12 papillary carcinomas, 4 follicular carcinomas, and 3 anaplastic carcinomas. The results were as follows: 1) The PCNA labeling indices in adenomatous goiter, follicular adenoma, and Hurthle cell tumor were 1.1, 1.5, and 2.4, respectively. They were significantly higher than the labeling index in normal thyroid. 2) The PCNA labeling indices in papillary carcinoma and follicular carcinoma were 3.5 and 4.4, respectively. They were significantly higher than the labeling indices in adenomatous goiter and follicular adenoma, but there was no significant difference between papillary and follicular carcinoma. 3) The PCNA labeling index in anaplastic carcinoma, 14.1, was significantly higher than those in benign and other malignant tumors. According to the results, the PCNA labeling index was well correlated with the malignant potential of a tumor. So the PCNA immunohistochemical staining is thought to be a useful method for the evaluation of the malignant potential and prognosis of a tumor.

The Study of Histopathologic Grade, PCNA and AgNORs Staining in the Recurrent Urinary Bladder Cancer.: Soo Yeon Cho, Woon Sub Han; Korean J Pathol. 1994;28(6):643-650.

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Abstract PDF: The prognosis of transitional cell carcinoma(TCC) of the urinary bladder is related to histopathologic parameters, among which the clinical stage and histopathologic grade are most important prognostic determiantors. Recently the immunohistochemical assessment of proliferating cell nuclear antigen(PCNA) and nucleolar organizer region number(AgNORs) can obtain the PCNA, and AgNORs stainings were studied in 55 the sequential biopsies of 22 recurrent TCCs of the urinary bladder. 6 cases showed the increased changes of grade, of which 5 cases was independently to the change of grade. The AgNORs in 18 cases showed increase in 10 cases. The comparison between PCNA count and AgNORs score according to grade was performed in the changes between grade II and III, both PCNA count and AgNORs score were increased with in crease of grade. However, The change of the PCNA count was stastically significant, but not AgNORs score.

Prognostic Value of the PCNA Index in Transitional Cell Carcinoma of the Urinary Bladder.: Sang Yeop Yi, Young Nyun Park, Chan Il Park; Korean J Pathol. 1994;28(3):282-287.

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Abstract: It is well known that histologic grade and tumor stage are important prognostic factors, and that the monoclonal antibody to proliferating cell nuclear antigen(PCNA) can recognize S-phase cells. The PCNA index of 53 transitional cell carcinomas(TCCs) of the urinary bladder was studied to evaluate its prognostic validity. The PCNA indices of TCCs ranged from 38 to 92, whih were quite different from that of normal transitional epithelium(9.4). The PCNA indices were significantly higher in tumors of the higher histologic grade and/or tumor stage(correlation coefficient 0.64 and 0.43; P=0.00). The PCNA index was particularly valuable in discriminating the superficial TCCs from the deeply invasive TCCs(67.1+/-15.46 and 79.9+/-9.70; P=0.000). Among TCCs of the same tumor stage, the histologic grade affected the PCNA index. However, TCCs of the same histologic grade revealed similar PCNA indices regardless of tumor stage. These results indicate that the PCNA index is an objective and reliable prognostic factor in TCCs, which is superior to the conventional histologic grade.

Pathological Analysis of 15 Cases of Phyllodes Tumors of the Breast.: Sung Nam Kim, Woo Ho Kim, Sang Kook Lee; Korean J Pathol. 1993;27(1):19-26.

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Abstract PDF: Retrospective clinicopathologic analysis of 15 patients with the phyllodes tumors(PT) of the breast, diagnosed at SNUH over 6 years period, was done. By light microscopy, 8 cases were diagnosed as benign, and 7 cases were diagnosed as malignant. Mean ages o the patients were 37 and 34 years in malignant and benign, respectively. Most of those cases were presented with a palpable mass of the breast. None of the patients with malignant PT had distant metastasis, Local recurrences were experienced in 3 patients among the malignant PT, and one patient among the benign PT. One of 7 malignant PT was coexisted with simultaneous ipsilateral infiltrating duct carcinoma. The clinical course was not well correlated with pathologic features. The prognostic significances of several histopathologic parameters were assessed for possible correlation with local recurrence, metastasis and death; stromal cellularity, stromal cellular atypism, mitotic activity, tumor contour, necrosis, tumor size and heterologous stromal elements. Immunohistochemistry using antibody to vimentin, proliferating cell nuclear antigen(PCNA) and epidermal growth factor receptor(EGF-R) were analysed. In the 5 cases of benign PT, the stromal cells stained diffusely positive for vimentin and 3 cases of malignant tumors show similar staining for vimentin. The percentage of PCNA-positive cells were higher in the malignant PT than in the benign ones; they were 3.5% to 60% in malignancy, while they were less than 60% in all benign PT. The results of EGF-R staining were correlated with the histologic classification; only 2 cases out of 8 benign PT show diffusely positive staining of EGF-R in the cytoplasm, but 6 cases out of 7 malignant PT show positive findings.

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.

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