GRB7 Gene Amplification In The Initial Clinical Analysis Of Ovarian Cancer Research

Objective: To evaluate whether it exists growth factor receptor-bound protein 7(GRB7) gene amplification in ovarian cancer tissues and the correlation between GRB7 gene amplification and its protein expression. In addition, we also investigated respectively the relationship existing among the two GRB7 status with regard to clinical-pathology emergence in OC patients. Further to verify whether there is GRB7 gene amplification in circulating tumor cells which were captured from the peripheral blood of the OC patients for the preliminary clinical analysis.Method: The GRB7 protein expression were detected through immunohistochemical(IHC) in a Tissue Microarray(TMA) which contained 90 cases of ovarian cancer(mainly is epithelial ovarian cancer, EOC) and 10 cases of normal ovarian tissues, and its relationship with some clinicopathologic characteristics of patients with ovarian cancer were analyzed;In another the same TMA to detect whether it exists GRB7 gene amplification through Fluorescence In Situ Hybridization(FISH) which is an experimental method with a GRB7 DNA fluorescence probe(red) used as experimental group and a centromere specific DNA fluorescence probe(green) for chromosome 17(CEP17) used as control group;To evaluate the correlation between GRB7 gene amplification and protein expression in ovarian cancer(OC) tissues;To capture and identify of circulating tumor cells(CTCs) in blood samples of OC patients;To verify whether there is GRB7 gene amplification in CTCs of OC patients.Results:The GRB7 protein expression by IHC analysis was observed in 52/90(57.8%) OC tissues with 3 cases(3.3%) scored 3+ and 9 cases(10%) scored 2+. The clinicopathologic factors analysis, such as age, histopathologic type, grade and FIGO stage, showed no significant correlation with GRB7 overexpression in OC tissues; Based on our findings we noticed that 6 cases(6/88; 6.8%) with GRB7 amplied in OC tissues which never appeared in normal ovarian tissue. The clinicopathologic factors analysis, such as age, histopathologic type, grade and FIGO stage, showed no significant correlation with GRB7 gene amplification in OC tissues; In OC tissues, all the six cases amplified by FISH appeared in diversified classes of IHC, containing 3+(three cases), 2+(one case), 1+(one case) and 0(one case). Over all, IHC and FISH results were statistically significantly correlated(Kappa = 0.651, P < 0.001); In blood samples of ovarian cancer patients 28(93.3%, 28/30) cases were detected and identified as circulating tumor cells(CTCs) ranging of 0-11/7.5ml. Above the median count(3.5/7.5m1) of ovarian cancer patients was 40%(12/30);It showed no significant correlation between CTCs count and the clinicopathologic factors, such as age, histopathologic type, grade, FIGO stage,and presence of surgery or chemotherapy in OC patients.In CTCs of OC patients,2 cases(6.7%,2/30) were detected GRB7 gene amplification, whose CTCs counts both were higher than the median, and both were high grade and III stage in serous OC patients;But there showed no significant correlation between GRB7 gene amplification and the clinicopathologic factors, such as age, histopathologic type, grade, FIGO stage, CTCs count, and presence of surgery or chemotherapy in OC patients.Conclusion: It really existed GRB7 gene amplification in OC tissues which had a good consistency and a close relationship with GRB7 protein overexpression;But the clinicopathologic factors analysis, such as age, histopathologic type, grade and FIGO stage, showed no significant correlation with GRB7 overexpression and its gene amplification. The CTCs detection rate is high in the peripheral blood of the OC patients.There were also a lower rate of GRB7 gene amplification in CTCs of the OC patients;however,there showed no significant correlation between GRB7 gene amplification or CTCs count and the clinicopathologic factors, such as age, histopathologic type, grade, FIGO stage, and presence of surgery or chemotherapy in OC patients,neither between the both.