Journal of Pathology and Translational Medicine

Original Articles

Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer: Wanlu Li, Mi-Ra Lee, EunHee Choi, Mee-Yon Cho; J Pathol Transl Med. 2017;51(1):17-23. Published online December 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.23

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Background
Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples.
Methods
We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling.
Results
The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133⁺ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133⁺ versus 4.231 ± 3.812 in CD133– (p = .034).
Conclusions
As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC.

Citations

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Antiapoptotic Gene Genotype and Allele Variations and the Risk of Lymphoma
Osama M. Al-Amer, Rashid Mir, Abdullah Hamadi, Mohammed I. Alasseiri, Malik A. Altayar, Waseem AlZamzami, Mamdoh Moawadh, Sael Alatawi, Hanan A. Niaz, Atif Abdulwahab A. Oyouni, Othman R. Alzahrani, Hanan E. Alatwi, Aishah E. Albalawi, Khalaf F. Alsharif,
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Cancers.2022; 14(21): 5180. CrossRef
EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer
Rokeya Akter, Kwangmin Kim, Hye Youn Kwon, Youngwan Kim, Young Woo Eom, Hye-mi Cho, Mee-Yon Cho
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Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts
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Obatoclax, a Pan-BCL-2 Inhibitor, Downregulates Survivin to Induce Apoptosis in Human Colorectal Carcinoma Cells Via Suppressing WNT/β-catenin Signaling
Chi-Hung R. Or, Chiao-Wen Huang, Ching-Chin Chang, You-Chen Lai, Yi-Ju Chen, Chia-Che Chang
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M1 Macrophages Promote TRAIL Expression in Adipose Tissue-Derived Stem Cells, Which Suppresses Colitis-Associated Colon Cancer by Increasing Apoptosis of CD133+ Cancer Stem Cells and Decreasing M2 Macrophage Population
Young Woo Eom, Rokeya Akter, Wanlu Li, Suji Lee, Soonjae Hwang, Jiye Kim, Mee-Yon Cho
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MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression
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Activated STAT3 may participate in tumor progression through increasing CD133/survivin expression in early stage of colon cancer
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Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats: Jae Chul Lee, Choong Ik Cha, Dong-Sik Kim, Soo Young Choe; J Pathol Transl Med. 2015;49(6):472-480. Published online October 16, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.11; Retraction in: J Pathol Transl Med 2016;50(4):325

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Review

Molecular Imaging in the Era of Personalized Medicine: Kyung-Ho Jung, Kyung-Han Lee; J Pathol Transl Med. 2015;49(1):5-12. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.24

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Abstract PDF

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

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Original Articles

Expression of DNA Topoisomerase II-alpha as a Proliferating Marker in Urothelial Carcinoma of Urinary Bladder based on World Health Organization/International Society of Urological Pathology Consensus Classification: A Correlation with Expression of Ki-67 and Apoptosis: Tae Jin Lee, Dong Ki Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2002;36(5):305-313.

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Abstract PDF: BACKGROUND
DNA topoisomerase II-alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relationship between the expression of DNA topoisomerase II-alpha as a proliferating marker, and the expression of Ki-67 and apoptosis in urothelial carcinoma of urinary bladder based on World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification.
METHODS
73 urothelial carcinomas of the urinary bladder after transurethral resection and 25 carcinomas after radical cystectomy were investigated for histologic grading based on WHO and WHO/ISUP consensus classification. Formalin fixed, paraffin embedded tissue of 98 specimens from 73 patients were immunohistochemically stained for DNA topoisomerase II-alpha and Ki-67, and in situ TdT-mediated dUTP-biotin nick end labeling method for evaluation of apoptotic cells was performed. For each case, a DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were determined.
RESULTS
The histologic grades of 73 cases based on the WHO grading system were 21.9% (16 cases) in grade 1, 65.8% (48 cases) in grade 2, and 12.3% (9 cases). 5.5% (4 cases) of papillary neoplasm of low malignant potential, 47.9% (35 cases) of urothelial carcinoma of low grade, and 46.6% (34 cases) in urothelial carcinoma of high grade were reclassified using the WHO/ISUP consensus classification. Histologic grades based on two grading systems were correlated to invasion and stage (p<0.05). DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were correlated to histologic grades based on two grading system and invasion. Also, the correlation of DNA topoisomerase II-alpha and Ki-67 indices, and DNA topoisomerase II-alpha and apoptotic indices were significant, respectively.
CONCLUSIONS
DNA topoisomerase II-alpha appears to be an useful marker for assessing the proliferation potential of urothelial carcinoma of in the urinary bladder.

Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma.: Kyung Hwa Lee, Soong Lee, Hyeon Min Lee, Seung Chul Back, Sung Bum Cho, Jae Hyuk Lee; Korean J Pathol. 2011;45(4):397-405.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.397

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Abstract PDF

BACKGROUND
The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance.
METHODS
Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method.
RESULTS
Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041).
CONCLUSIONS
Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

Citations

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A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer
Pierina Cetraro, Julio Plaza-Diaz, Alex MacKenzie, Francisco Abadía-Molina
Cancers.2022; 14(7): 1671. CrossRef

Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.: Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee; Korean J Pathol. 2010;44(3):252-258.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252

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Abstract PDF

BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.

Citations

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Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef
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Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
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Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef

Expression of Survivin in Gastric Carcinoma and its Relation to Tumor Cell Proliferation and Apoptosis.: Wan Sik Lee, Sung Bum Cho, Jong Sun Rew, Jae Hyuk Lee, Chang Soo Park, Young Eun Joo; Korean J Pathol. 2009;43(4):329-334.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.329

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Abstract PDF

BACKGROUND
Survivin, a novel antiapoptotic gene has been linked with tumor development and progression in various human carcinomas including gastric carcinomas. The aim of this study was to evaluate the expression of survivin in gastric carcinoma and its correlation with tumor cell proliferation and apoptosis. METHODS: Expression of survivin was evaluated immunohistochemically in 84 surgically resected gastric carcinomas. Tumor cell apoptosis was evaluated with terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and Ki-67 immunostaining was used for evaluation of tumor cell proliferation. RESULTS: Expression of survivin was noted in 53.6% of the gastric carcinomas, and was significantly associated with depth of invasion, status of lymph node metastasis or tumor stage (p=0.022, 0.034, 0.040, respectively). There was an inverse correlation between survivin expression and apoptotic index (p=0.015). But there was no significant correlation between survivin expression and Ki-67 labeling index (p=0.430). CONCLUSIONS: These results suggest that survivin expression may contribute to tumor development and progression by inhibiting apoptosis in human gastric carcinoma.

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Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression
SOO-AH KIM, RAN HONG
Oncology Letters.2014; 7(5): 1589. CrossRef

Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.: Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon; Korean J Pathol. 2009;43(4):317-320.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.

Melanosis Coli: Relation to Apoptosis in Pathogenesis.: Sun Hee Sung, Hea Soo Koo, Woon Sup Han; Korean J Pathol. 1996;30(7):570-575.

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Abstract PDF: Melanosis coli is characterized by a dark brownish discoloration of the colonic mucosa. Its pathogenesis is still unknown. Recently it was proposed that the apoptosis of mucosal epithelium due to habitual use of laxatives play an important role for induction of melanosis coli. We studied clinicopathologic aspects of 12 cases of melanosis coli and analysed the histochemical and immunohistochemical characteristics of them. Results are as follows. : Mean patient's age was 53.5, and the male:female ratio was 4:8. Nine patients had a history of constipation, and all of these had administrated various kinds of laxatives. The severity of discoloration was correlated with the duration of constipation and age. There was no difference of anatomical distribution in colon. Other remarkable mucosal lesions were not accompanied. On pathologic examination, all cases showed frequent yellow-brown pigment laden cells in lamina propria. These pigments were positive for periodic acid Schiff stains, Fontana Masson stains, and Victoria blue stains, however they were negative for prussian blue stain. On immunohistochemical stainings pigmented cells were positive for CD68, and negative for S-100 protein and neuron specific enolase. These results indicate that they are macrophages. On ultrastructural examination pigmented cytoplasms were filled with variable sized electron dense granules including irregulary round deformed membranous structures, lipid vacuoles. Apoptosis of mucosal epithelium was noted in 5 cases. These findings suggest that apoptosis is the significant pathologic process in the progression of some cases of melanosis coli.

Morphological and Biochemical Study on the Processes of Apoptosis Induced by Radiation.: Kye Yong Song, Seong Man Kang, Seong Hwan Ha, Sang Chul Park; Korean J Pathol. 1996;30(9):819-829.

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Abstract PDF: Transglutaminase(TGase) is a calcium dependent enzyme that catalyse and acyl transfer reaction forming epsilon-(gamma-glutamyl)-lysine cross linkage. the major known effect of TGase is its important role in the programmed cell death manifested in the granular layer of the skin and acidophilic bodies in the viral hepatitis and neoplastic processes. The enzyme activity, immunohistochemical reaction using polyclonal antibodies against cytosolic TGase C, light and electron microscopic studies and TdT staining of the transplanted fibrosarcoma cells in C3H mouse with radiation therapy were done. The presence of TGase was detected immunohistochemically by avidin-biotin peroxidase complex (ABC) method Apoptosis were significantly induced after irradiation dependent with time factors and irradiation doses, resulted in marked and confluent tumor cell loss. Highest activity of the cytosolic form of TGase was noted at 24 hours and decrease after then while membrane bounded form of the TGase showed no significant changes. Immunohistochemical staining revealed strong positive reaction in the sarcoma cells in diffuse fasion and around the necrotic foci in the cytoplasm. Terminal dideoxynucleotidyl transferase(TdT) staining revealed increasing numbers of apotptic cells from two hours after irradiation. In the mechanism of decreasing tumor size and cell death in radiation therapy, apoptosis plays an important role and during that process transglutaminse might do some irreversible cross-linking effects of cytoplasmic proteins causing cell death in part.

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Correlation Between the Frequency of Apoptotic Bodies and Gleason Scores in Prostatic Cancer.: Hee Soo Yoon, Ho Jung Kim, Hea Soo Koo, Ok Kyung Kim, Sung Sook Kim; Korean J Pathol. 1997;31(5):462-469.

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Abstract PDF: Apoptosis (or programmed cell death) is defined by morphologic changes induced by a spectrum of physical and chemical agents. resulting in non-pathologic cell loss, which is relevant to a range of biological processes, including differentiation, development, maturation, and injury of cells as well as immunologic function. In this study, we examined the frequency of apoptotic bodies and mitoses (apoptotic and mitotic indices) in the tissue samples of 35 patients of prostatic carcinoma, which were grouped according to the Gleason scores, and 5 cases of benign prostatic hyperplasia. The indices were determined as the numbers of apoptotic and mitotic bodies per 100 tumor cells in hematoxylin eosin stained section. The apoptotic bodies were confirmed by the in situ nick end labelling method. The apoptotic and mitotic indices were observed more frequently in prostatic carcinoma than the benign hyperplastic prostatic tissues with a positive correlation between the frequency of apoptotic bodies and Gleason scores in prostatic cancer. In conclusion, an increased programmed cell death was correlated with the increasing malignant potential (higher Gleason scores) in prostatic cancer.

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.

Immunohistochemical Study on the Expression of Bcl-2 and p53 Protein in Gastric Adenocarcinoma.: Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1997;31(12):1282-1290.

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Abstract PDF: This study was carried out to investigate the immunohistochemical expression of bcl-2 and p53 protein in the intestinal type and the diffuse type of gastric adenocarcinoma by Lauren's classification. A total of 100 cases, including 50 cases of the intestinal type and 50 cases of the diffuse type from paraffin embedded gastrectomy specimens, were immunohistochemically stained for bcl-2 and p53 protein. Bcl-2 protein was expressed in 38% (19/50) of intestinal type and 30% (15/50) of diffuse type. The incidence of bcl-2 protein expression was higher in the intestinal type than in the diffuse type, but no significant correlation was present (p>0.05). p53 protein was expressed in 68% (34/50) of the intestinal type and 60% (30/50) of the diffuse type. The incidence of p53 protein expression was higher in the intestinal type than in the diffuse type, but no significant correlation was present (p>0.05). And an expression of bcl-2 and p53 protein did not correlate with depth of invasion, lymph node meatastasis and TNM stage, respectively (p>0.05). These results suggest that bcl-2 and p53 gene alteration appear to play a more important role in the carcinogenesis of the intestinal type than the diffuse type. However, there is no significant difference between the intestinaPU: The Korean Society of Pathologistsl type and the diffuse type in bcl-2 and p53 protein expression.

Taxol-induced Pathological Findings in Rat Small Intestine.: Sun Hee Chang, Shi Nae Lee, Hee Soo Yoon, Min Sun Cho, Hea Soo Koo, Woon Sup Han; Korean J Pathol. 1997;31(12):1291-1296.

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Abstract PDF: Taxol is an active chemotherapeutic agent against a variety of solid tumors and a potentially useful drug for augmenting the cytotoxic action of radiotherapy against certain cancers. Taxol blocks cells in the mitotic phase of cell cycle. The aim of this study was to define the in vivo response of rapidly dividing cells of the small intestinal mucosa to taxol. We studied the numbers of apoptotic and mitotic cells and the expression of bcl-2 and p53 in rat jejunal crypt cells at 1, 2, 4, 8, 12, 16, and 24 hours and 3 and 5 days after intraperitoneal injection of taxol. Mitosis peaked at 2 and 4 hours and 12 and 16 hours. Apoptosis peaked at 16 hours and returned to normal after five days. The glands in crypts showed marked distortion with atypical lining cells after three days, which returned to normal at 5 days. bcl-2 expression was markedly decreased at 8 to 24 hours and subnormally recovered after three to five days. p53 showed no significant changes throughout. The histopathological changes in small intestine due to taxol were transient with complete recovery. bcl-2 expression was inversely corresponded to numbers of apoptosis. The changes were p53 independent. Further studies to understand the conditions that maximize the cell-cycle modulating effects of taxol cl-may greatly enhance its anti-tumor effectiveness.

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