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)