Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance

Journal of Experimental & Clinical Cancer Research, Jun 2013

Objective This study investigates the expression of Lewis y antigen, integrin αv, β3 in epithelial ovarian cancer tissues. We further evaluate the relationship between their expression and chemotherapy resistance of ovarian cancer and its possible clinical significance. Methods Tissues of 92 patients with ovarian cancer meeting the inclusion criteria with complete follow-up data were enrolled and divided into chemotherapy resistant group and sensitive group. The expression and relationship of Lewis y antigen and integrin αv, β3 are assessed in paraffin sections using immunohistochemistry and double-labeling immunofluorescence method. Multivariate logistic regression analysis was used to investigate the relationship between age, clinical stage, differentiation, histologic subtype, Lewis y antigen and integrin αv, β3 expression in ovarian cancer patients. Results The expression rates of Lewis y antigen and integrin αv in the resistant group, significantly higher than the rates found in the sensitive group (p <0.05). Multivariate analysis showed that the expression of Lewis y antigen, integrin αv and ovarian cancer’s clinical stage were independent, drug resistance-related risk factors. The expression levels of Lewis y antigen and integrin αv, β3 were positively correlated with each other. Conclusions A close correlation between Lewis y antigen, integrin αv, β3 and ovarian cancer was observed. Lewis y antigen can influence the biological behavior of a tumor cell as an important composition of integrin αv, β3 by some signal pathway. And the expression of Lewis y antigen, integrin αv and ovarian cancer’s clinical stage are both independent, drug resistance-related risk factors.

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Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance

Journal of Experimental & Clinical Cancer Research Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance Jian Gao 0 Zhenhua Hu 0 Dawo Liu 0 Juanjuan Liu 0 Chuan Liu 0 Rui Hou 0 Song Gao 0 Danye Zhang 0 Shulan Zhang 0 Bei Lin 0 0 Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University , Shenyang 110004 , China Objective: This study investigates the expression of Lewis y antigen, integrin αv, β3 in epithelial ovarian cancer tissues. We further evaluate the relationship between their expression and chemotherapy resistance of ovarian cancer and its possible clinical significance. Methods: Tissues of 92 patients with ovarian cancer meeting the inclusion criteria with complete follow-up data were enrolled and divided into chemotherapy resistant group and sensitive group. The expression and relationship of Lewis y antigen and integrin αv, β3 are assessed in paraffin sections using immunohistochemistry and doublelabeling immunofluorescence method. Multivariate logistic regression analysis was used to investigate the relationship between age, clinical stage, differentiation, histologic subtype, Lewis y antigen and integrin αv, β3 expression in ovarian cancer patients. Results: The expression rates of Lewis y antigen and integrin αv in the resistant group, significantly higher than the rates found in the sensitive group (p <0.05). Multivariate analysis showed that the expression of Lewis y antigen, integrin αv and ovarian cancer's clinical stage were independent, drug resistance-related risk factors. The expression levels of Lewis y antigen and integrin αv, β3 were positively correlated with each other. Conclusions: A close correlation between Lewis y antigen, integrin αv, β3 and ovarian cancer was observed. Lewis y antigen can influence the biological behavior of a tumor cell as an important composition of integrin αv, β3 by some signal pathway. And the expression of Lewis y antigen, integrin αv and ovarian cancer's clinical stage are both independent, drug resistance-related risk factors. Ovarian Cancer; Lewis y Antigen; Integrin αv; β3; Chemotherapeutic Drug Resistance Background Ovarian cancer has the highest mortality rate of all cancers of the female reproductive system. Chemotherapy resistance is an important factor influencing treatment efficacy. In recent years, studies have shown that through the interaction between surface adhesion molecules and surrounding extracellular matrix, tumor cells can promote proliferation, invasion, and metastasis, thus improving their tolerance to chemotherapeutic drugs [ 1 ]. Cell adhesion-mediated drug resistance (CAM-DR) is a relatively new theory for the mechanism of drug resistance in tumor cells [ 2-4 ]. Integrins comprise a large family of cell adhesion molecules; they are transmembrane glycoproteins that play a key role in the interaction between cells and components of the interstitial space. Integrin-mediated interactions between cells or between cells and the extracellular matrix play an important role in tumor growth, invasion, metastasis, drug resistance, and many other processes [ 5 ]. Many studies have confirmed that carbohydrate antigens on the cell surface are closely related to integrins. In our previous work, we have found that as a part of the integrin αvβ3 structure, Lewis y antigen expression is related to the degree of invasiveness of ovarian cancer [ 6 ]. Here we use immunohistochemistry to further study the expression of Lewis y antigen and integrin αvβ3 in tissue specimens from patients with chemotherapy resistant or sensitive ovarian cancer and analyze how the expression of these molecules correlates with chemotherapy resistance and the resulting clinical significance. Materials and methods 92 chosen paraffin samples are obtained from the operations done from 2006 to 2010 in the department of Gynecology and Obstetrics of Sheng Jing Hospital Affiliated to China Medical University. After the cytoreductive surgery and 6-8 periods of systematic chemotherapy, each patient will receive a follow up observation for at least one year. Among the 92 cases of primary epithelial ovarian cancer studied, there are 58 cases of serous cystadenocarcinoma, 8 mucinous cystadenocarcinoma, 4 endometrioid carcinoma, 7 clear cell carcinoma and 15 poorly differentiated adenocarcinoma. According to histological grade, there were 15 cases of high differentiated, 35 moderate and 42 poor. The group includes 19 cases of stages I, 13 stages II, and 60 stages III (according to International Federation of Gynecology and Obstetrics (FIGO) criteria). All the cases are primary, the information and follow-up data are complete; chemical treatment is not used in all the patients before operations. Drug resistance related clinical and pathological parameters Tissues obtained between 2006 and 2010 from 92 patients with ovarian cancer meeting the inclusion cri (...truncated)


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Jian Gao, Zhenhua Hu, Dawo Liu, Juanjuan Liu, Chuan Liu, Rui Hou, Song Gao, Danye Zhang, Shulan Zhang, Bei Lin. Expression of Lewis y antigen and integrin αv, β3 in ovarian cancer and their relationship with chemotherapeutic drug resistance, Journal of Experimental & Clinical Cancer Research, 2013, pp. 36, 32, DOI: 10.1186/1756-9966-32-36