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Expression of E-cadherin,beta-catenin,cathepsin D,gelatinases and their inhibitors in invasive ductal breast carcinomas

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Chinese Medical Journal 2007年第18期120卷 1597-1605页

作者： ZHANG Yun-gang DU Juan TIAN Xin-xia ZHONG Yan-feng FANG Wei-gang Department of Pathology Peking University Health ScienceCenter Beijing 100083 China

Background E-cadhedn, beta-catenin, cathepsin D, matrix metalloproteinase （MMP）-2, MMP-9, tissue inhibitors of metalloproteinase （TIMP）-1 and TIMP-2 are all invasion-related proteins. The expression patterns of these proteins in invasive ductal breast carcinomas, and their associations with known clinicopathological parameters, tumor recurrence and expressions of estrogen receptor （ER）, progesterone receptor （PR）, PS2 and c-erbB2 were not well studied in Chinese patients, Methods In a set of 94 invasive ductal breast carcinomas, protein expressions of these molecular markers were investigated by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence and expressions of ER, PR, PS2 and c-erbB2 were also examined. In addition, the interrelationship between the expressions of these proteins were studied. Results Preserved membrane E-cadherin expression was associated with late tumor stage and tumor recurrence, whereas the reduced junctional beta-catenin associated with positive lymph node status and c-erbB2 overexpression. Positive staining of cathepsin D in tumor stromal cells displayed a significant association with late tumor stage. High expression of MMP-2 in cancer cells was associated with large tumor size and PR positive expression. TIMP-2 expression was positively associated with tumor recurrence. In addition, inter-relationship between the expressions of these biomarkers was also assessed, Cathepsin D staining in cancer cells was inversely correlated with its staining in stromal cells, and also inversely correlated with MMP-2 staining in tumor stromal cells. MMP-2 expression in stromal cells displayed an inverse correlation with TIMP-2 expression. MMP-9 expression displayed parallel associations with TIMP-1 and TIMP-2 expression. Conclusion Evaluation of E-cadherin, beta-catenin, cathepsin D, MMP-2 and TIMP-2 expression may be of some help in more accurately predictinq the pro qnosis of invasive ductal

关键词： ductal breast carcinomas E-cadherin beta-catenin cathepsin D matrix metalloproteinase 2

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Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers

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World Journal of Gastroenterology 2008年第39期14卷 6052-6059页

作者： Worrawit Wanitsuwan Samornmas Kanngurn Teeranut Boonpipattanapong Rassamee Sangthong Surasak Sangkhathat Tumor Biology Research Group and Department of Surgery Faculty of MedicinePrince of Songkla UniversityThailand Tumor Biology Research Group and Department of Pathology Faculty of MedicinePrince of Songkla UniversityThailand Tumor Biology Research Group and Epidemiology Unit Faculty of MedicinePrince of Songkla UniversityThailand

AIM： To examine the expression of beta-catenin in colorectal cancer and look for association with other dinico-pathological parameters. METHODS;： Tumor samples from 163 cases of colorectal cancer （CRC） who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density （OSD） and percentage of cells having nuclear localization was counted as nuclear staining density （NSD）. Univariate exploration used log-rank test and multivariate survival analysis used Cox＇s hazard regression model. RESULTS： beta-catenin immunoreactivity was detected in 161 samples （98.8%）, of which 131 cases had nuclear staining. High OSD （≥ 75%）, detected in 123 cases （75.5%）, was significantly associated with earlier clinical staging （P 〈 0.01）, lower nodal status （P = 0.02）, non-metastatic status （P 〈 0.01） and better differentiation （P = 0.02）. Multivariate analysis found that high OSD was independently associated with better survival [Cox＇s hazard ratio 0.51, 95% confidence interval （CI） 0.31-0.83]. Although high NSD （≥ 75%） was correlated with high pre-operative serum CEA （P = 0.03）, well differentiation （P 〈 0.01）, and increased staining intensity（P 〈 0.01）, the parameter was not significantly associated with survival. CONCLI3SIOM： Unlike previous reports, the study did not find a predictive value of nuclear beta-catenin in CRC. Instead, the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover, the parameter also independently predicted superior survival.

关键词： Colorectal carcinoma beta-catenin CTNNB1 Wnt-signaling pathway Prognosis

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E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

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World Journal of Gastroenterology 2007年第29期13卷 3925-3931页

作者： Chihaya Koriyama Suminori Akiba Tetsuhiko Itoh Kazunobu Sueyoshi Yoshie Minakami Alejandro Corvalan Suguru Yonezawa Yoshito Eizuru Department of Epidemiology and Preventive Medicine Kagoshima University Graduate School of Medical and Dental Sciences 8-35-1 Sakuragaoka Kagoshima Japan Geriatric Health Services Facility 551 Akasegawa Akune Kagoshima Japan Kazunobu Sueyoshi Department of Pathology Kagoshima City Hospital 20-17 Kajiya-cho Kagoshima Japan Division of Oncogenic and Persistent Viruses Center for Chronic Viral Diseases Kagoshima University Graduate School of Medical and Dental Sciences 8-35-1 Sakuragaoka Kagoshima Japan Department of Anatomic Pathology P. Catholic University Santiago Chile Department of Human Pathology Kagoshima University Graduate School of Medical and Dental Sciences 8-35-1 Sakuragaoka Kagoshima Japan

AIM： To examine the role of E-cadherin and betacatenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas （EBV-GCs）. METHODS： We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients＇ prognosis and the expressions of these proteins. RESULTS： Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta- catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 950 confidence interval （CI）, 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequently in EBV-GCs than non-EBV-GCs （odds ratio = 2.23; 95% CI, 0.97-5.09）, and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs （P = 0.024）. Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis （P 〈 0.001）. Among EBV- GCs, the depth of invasion （P = 0.005）, lymph node metastasis （P = 0.004） and an intestinal type by Lauren classification （hazard ratio = 9.47; 95% CI, 2.67-33.6） were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC （hazard ratio = 0.32; 95% CI, 0.11-0.93）. CONCLUSION： We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV- GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

关键词： Epstein-Barr virus Gastric carcinoma E-cadherin beta-catenin Prognosis

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Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

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World Journal of Gastroenterology 2007年第18期13卷 2622-2625页

作者： Lv Ji Xiu-Feng Cao He-Ming Wang Yi-Sheng Li Bin Zhu Jian Xiao Dan Wang Affillted Nanjing First Hospital NanjingMedical University Nanjing 210006 Jiangsu Province China

AIM： To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma （ESCC）. METHODS： beta-catenin mRNA expression level in 40 ESCC patients （28 males and 12 females, age range 38-82 years, median 60 years） was analyzed by real- time PCR. beta-catenin mRNA expression levels in tumor cells were categorized as weaker （level 1） or equal to or stronger （level 2） than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS： Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis （0.0776±0.0369 vs 0.3413±0.1803, P 〈 0.001） and deeper tumor invasion （0.0751±0.0356 vs 0.3667±0.1928, P 〈 0.001）, and a poorer survival rate （P = 0.0024） than ESCC with level I expression. CONCLUSION： beta-catenin expression in ESCC is of great importance.

关键词： beta-catenin mRNA expression level Esophageal carcinoma Prognosis

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Expressions of GSK-3beta,beta-catenin and PPAR-Gamma in Medulloblastoma

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Chinese Journal of Cancer Research 2009年第3期21卷 235-239页

作者： Xiong Zhang Lu Si Yu Li Can Mi Institute of Neuroscience Chongqing Medical University Chongqing 400016 China Department of Pathology Chongqing Medical University Chongqing 400016 China

Objective： To investigate the expressions of GSK-3beta, beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application. Methods： Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues. Results： The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal （P〈0.05）. Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation. Conclusion： Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

关键词： Gsk-3beta beta-catenin PPAR-gamma Medulloblastoma

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Expression of beta-catenin and APC Protein in Ovarian Epithelial Tumor and Its Implication

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Chinese Journal of Cancer Research 2007年第1期19卷 72-75页

作者：林晓李昱米粲 Department of Pathology Chongqing University of Medical Science

Objective： To investigate the expression of beta-catenin, APC protein and its implication in ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and APC protein in 48 cases of ovarian epithelial tumor. Results： The abnormal expression rates of beta-catenin in ovarian malignant and borderline epithelial tumors were higher than that in benign epithelial tumors. The expression of APC protein in benign epithelial tumors was significantly greater than that in malignant epithelial tumors. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors. Conclusion： beta-catenin and APC protein have important effect on pathogenesis and development of ovarian epithelial tumors.

关键词： beta-catenin APC protein Ovarian epithelial tumors

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Expressions of beta-catenin,E-cadherin and MMP-7 in Ovarian Epithelial Tumors

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Chinese Journal of Cancer Research 2008年第3期20卷 190-193页

作者：林晓李昱米粲 Department of Pathology Chongqing University of Medical Sciences

Objective： To investigate the expressions of beta-catenin, E-cadherin and MMP-7 and their implications in ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, E-cadherin and MMP-7 in ovarian epithelial tumor in 66 cases. Results： The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumor was higher than those in borderline and benign epithelial tumors （P〈0.05）. The positive rates of E-cadherin in benign and borderline ovarian epithelial tumors were significantly greater than that in malignant epithelial tumor. The expression rates of MMP-7 in malignant and borderline ovarian epithelial tumors were higher than that in benign epithelial tumor （P〈0.05）. Conclusion： The abnormal expressions of beta-catenin, E-cadherin and MMP-7 might be used to indicate the malignance transform of ovarian epithelial tumors, but they have no significant correlation with peritoneal dropsy invasion, caul invasion and appendant invasion in ovarian epithelial tumor.

关键词： beta-catenin E-cadherin MMP-7 Ovarian epithelial tumor

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Expression of Wnt-1,beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

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Chinese Journal of Cancer Research 2008年第1期20卷 73-76页

作者：林晓胡琢瑛 Department of Pathology Chongqing University of Medical Science

Objective： To investigate the expression of Wnt-1, beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1, beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary. Results： The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell （P〈0.05）. The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell （P〈0.05）. A significant positive correlation was found between Wnt-1, beta-catenin and c-myc in malignant ovarian epithelial tumor （P〈0.05）. A significant difference of expressions of beta-catenin and C-myc was found between serous and mucinous tumors （P〈0.05）. Conclusion： The abnormal expression of Wnt-1, beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.

关键词： Wnt-1 beta-catenin c-myc Ovarian malignant epithelial tumors

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Relationship between Expression of beta-catenin and VEGFs(VEGFA,VEGF-C),VEGF Receptors-2(VEGFR-2)in Medulloblastoma

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Chinese Journal of Cancer Research 2008年第1期20卷 44-48页

作者：张红梅张雄李昱米粲 Department of Pathology Chongqing University of Medical science

Objective： To investigate the expression of beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGF receptor-2 （VEGFR-2） protein in medulloblastoma. Methods： Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues. Results： The expression rate of beta-catenin, and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue. A significant positive correlation was found between beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 protein in medulloblastoma. Conclusion： There was a correlation between beta-catenin and VEGFs （VEGF-A, VEGF-C） and VEGFR-2 in medulloblastoma, which may play a role in the pathogenesis and development of medulloblastoma.

关键词： beta-catenin VEGFs (VEGF-A, VEGF-C) and VEGFR-2 Medulloblastoma

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Disordered beta-catenin expression and E-cadherin/CDH1 promoter methyiation in gastric carcinoma

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World Journal of Gastroenterology 2006年第26期12卷 4228-4231页

作者： Li Wang Fan Zhang Ping-Ping Wu Xu-Cheng Jiang Lin Zheng Ying-Yan Yu Department of Pathology School of Medicine Shanghai Jiaotong University Shanghai 200025 China

AIM： TO investigate the distribution of beta-catenin in nuclei or membrane/cytoplasm of gastric carcinoma cells, the relationship between E-cadherin gene methylation and its expression, and the role of beta-catenin and E-cadherin as potential molecular markers in predicting tumor infiltration. METHODS： Twenty-nine cases of gastric carcinoma, classified as diffuse and intestinal variants, were selected for study. Nuclear and cytoplasmic proteins were purified and beta-catenin content was detected by ELISA. DNA methylation of E-cadherin/CDH1 gene promoter was studied by methylation-specific PCR and compaired with E-cadherin expression detected by immunohistochemistry. RESULTS： In 27 cases of gastric carcinoma, the ratio of beta-catenin content between nuclei and membrane/ cytoplasm was correlated with the T-classification （r = 0.392, P = 0.043）. The significance was present between T2 and T3 groups. No correlation was detected between diffuse and intestinal variants in terms of their betacatenin distribution. In 21 cases of diffuse variants of gastric carcinoma, there was a difference in E-cadherin expression between CDH1 gene-methylated group and non-methylated group （29 % vs 71%, P = 0.027）. No correlation between CDH1 gene methylation and T-classification was found, neither was the significance between E-cadherin expression and tumor infiltration grade. CONCLUSION： Comparative analysis of nuclear and membrane/cytoplasmic beta-catenin can predict local tumor infiltration. E-cadherin/CDH1 gene methylation is an important cause for its gene silence in diffuse variant gastric carcinoma. Methylation of CDH1 gene in the absence of E-cadherin is an early event in gastric carcinogenesis.

关键词： Gastric carcinoma beta-catenin E-cadherin DNA methylation

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