Correlations between Her2 oncoprotein, VEGF expression, MVD and clinicopathological parameters in gastric cancer.

Introduction: Gastric carcinoma is one of the most common malignancies worldwide and is the second most frequent cause of cancer deaths. Several molecular factors are studied as prognostic and predictive factors for gastric cancer, VEGF and Her2 being currently in the spotlight. The aim of the study was to estimate the expression of Her2, VEGF and the MVD in gastric carcinoma and its relationship to clinicopathological and biological features of the tumors.

Materials And Methods: In this study were included 28 patients with gastric carcinoma, of which 16 patients underwent total gastrectomy, which provided the TNM stage, and 12 patients with gastric biopsy. The gastric biopsies and the surgical samples were processed immunohistochemically using anti-Her2, anti-CD31, anti-CD34 and anti-VEGF antibodies.

Results: Her2 oncoprotein was overexpressed in 85.71% of intestinal type gastric cancer cases and 14.29% in diffuse type (p=0.01), and also more in stage I an II comparatively with stage III and IV (p=0.13). Her2 positive tumors were significant low grade (G1/G2) (p<0.01). MVD is higher in Her2 positive tumors than in the negative ones but not statistically significant (p=0.29 for CD31 and p=0.52 for CD34). Positive immunoreaction of VEGF was observed in 55.5% of the intestinal type carcinomas and in 80% of diffuse type. The correlation between expression of VEGF and TNM stage showed that this angiogenic factor is more frequent positive in the first two stages comparative with the IIIrd and IVth stages. The expression of VEGF is more frequent in G1-G2 tumors (p=0.003).There was a close relationship between tumor vascularity detected with CD34 and two main histological parameters: tumor type according to Lauren's classification (diffuse type; p=0.04) and tumor grade (well and moderately differentiated tumors; p=0.01). There was also a significant correlation of mean CD34 MVD value and the TNM stage being more expressed in stage III/IV than in I/II stages (p=0.004). The mean CD34 MVD value of VEGF positive tumors was 30.8 and was a significantly higher MVD than that of VEGF negative tumors (p<0.05).

Conclusions: Overexpression of Her2, the selecting factor of patients that benefit from a specific therapy, occurs at a significant frequency in gastric carcinomas, especially in intestinal type. The correlation between VEGF expression and CD34 MVD suggest that two molecular biomarkers play a major role in the biological tumor behavior and are able to be used as important prognostic parameters, which predict the aggressiveness of gastric carcinomas.