Investigation of the relation of her-2 gene expression and c-met expression in gastric cancers with histopathological prognostic parameters

ABSTRACT INVESTIGATION OF THE RELATION OF HER-2 GENE EXPRESSION AND c-MET EXPRESSION IN GASTRIC CANCERS WITH HISTOPATHOLOGICAL PROGNOSTIC PARAMETERS AIM: In this study, it was aimed to determine the frequency of HER-2 positivity in gastric carcinoma cases, to evaluate the consistency of increased HER-2 expression with immunohistochemical and silver in situ hybridization (SISH) methods and to show the relation with histopathological prognostic factors. Additionally, in the light of recent treatment approaches, we aimed to determine the expression frequency of c-MET, its relation with histopathological prognostic factors and HER-2 expression. MATERIALS AND METHODS: In our department, 203 cases with gastric cancer diagnosed in gastrectomy materials between 1996-2016 were included in the study. The findings included in the pathology report such as age and sex, location and size of the tumor, histological type, invasion depth, perineural invasion, lymphovascular embolism, lymph node metastasis, local invasion or distant metastasis were recorded. The evaluation of HER-2 immunohistochemistry (IHC) score was done as 0, 1+, 2+ and 3+ according to the scientific literature. HER-2 score of 2+ and 3+ cases were considered positive. In these cases, amplification was investigated by applying dual silver in situ hybridization (SISH)/IHK method. In addition, 40 cases evaluated as negative (0/1 +) with HER-2 and all cases with positive (2/3+) HER-2 immunohistochemically were stained with c-MET; the findings were compared with histopathologic factors and HER-2 positivity. RESULTS: All cases were stained with HER-2 as IHC and the positivity was found in 19.2% of them. Amplification was detected in 70% of 2+ cases and in 94.7% of 3+ cases by Dual SISH / IHC method (p≤0.05). With Dual SISH/IHC method, 80% of our HER-2 2+ cases (16/20) were weakly stained or unstained immunohistochemically. Statistically, HER-2 positivity was found associated only with intestinal type morphology (p=0,039). c-MET positivity was found in 19.2% of 79 cases. HER-2 (-) cases were found to show more c-MET (+) (57.4%) than HER-2 (+) (%34,4) cases and this was statistically significant (p=0,044). Statistically, c-MET positivity was found associated only with distal localization (p=0,038). HER-2+/c-MET+ co-expression was observed in %34,4 (11/32) of the cases. Comparisons were made between HER-2+/c-MET+ co-expression group and the remaning expression groups (HER-2+/c-MET-, HER-2-/c-MET+ and HER-2-/c-MET- groups respectively) for histopathological factors, but no statistically significant association were observed probably as a consequence of limited cases. CONCLUSIONS: In our study, it was determined that HER-2 positive tumors showed more intestinal morphology and c-MET positive tumors showed more distal localization. It has been shown that the Dual SISH/IHK method can provide ease of use if optimized. The presence of c-MET positivity (34.4%) observed in cases with HER-2 expression, suggests that c-MET may be responsible for some of the resistance to Trastuzumab treatment in these cases. Furthermore, it has been suggested that scoring criteria should be standardized in order to make a better explain the relation between c-MET and histopathologic prognostic factors, and to develop targeted therapies.