Assessment of CD105, α-SMA and VEGF expression in gastric carcinomas.

In this study, we analyzed the microvessel density (MVD) for CD105+ and α-SMA+ vessels and the VEGF immunoexpression in 38 gastric carcinomas. CD105+ MVD had superior values at the advancing edge compared with the intratumoral area, no matter of the analyzed clinico-pathological parameters, the difference being significant only in intestinal type, moderate differentiated carcinomas as well as in T2-T3 carcinomas, without lymph node metastases (p<0.05). Intratumoral expression of CD105+ MVD indicated significant differences related to histological type (p=0.006), depth of invasion (p=0.027) and lymph node metastases (p=0.009), but without statistical association in case of the advancing edge or metastases. The assesses of α-SMA+ MVD indicated no differences between intratumoral and advancing edge areas, no matter of the analyzed parameters, excepting intestinal type carcinomas, which presented significant high values (p=0.003) at the advancing edge. VEGF score revealed significant differences related to histological type (p=0.020), differentiation degree of the intestinal type carcinomas (p=0.036) and depth of invasion (p=0.049). In case of metastases, the levels of VEGF expression were higher in the primary tumor, without statistically significant differences (p>0.05). It were significant differences of intratumoral VEGF expression depending on CD105+ MVD values (p=0.019), but not with α-SMA+ MVD (p>0.05). Angiogenesis evaluated through the VEGF and MVD (CD105+ and α-SMA+) expression is correlated with the progression and metastasis of gastric cancer and could be considered a prognostic marker of these tumors.

Immunohistochemical expression of TGF beta (TGF-ß), TGF beta receptor 1 (TGFBR1), and Ki67 in intestinal variant of gastric adenocarcinomas.

Although in the last decades the incidence of gastric cancer declined, at present it is ranked worldwide on the fourth place between all human cancer pathology. Also, it has an aggressive behavior, the majority of patients being diagnosed in advanced stages. One of the key factors to control survival improvement of those patients is to clarify the molecular mechanisms involved in initiation, progression, invasion, and metastasis of gastric cancer. We thus investigated the immunoreactivity for TGF-ß, TGFBR1, and Ki67 of 25 specimens of intestinal gastric adenocarcinomas, and compared this with the correspondent reactivity for three specimens of diffuse gastric carcinomas; in the end, we tried to establish a statistical correlation with major clinicomorphological parameters. As a result, we noticed that the highest reactivity was present in the diffuse type compared with the intestinal variant, in which the TGF-ß reactivity progressively increased along the normal epithelium-intestinal metaplasia-dysplasia-carcinoma sequence. Also, we found for intestinal variant that TGF-ß immunoreactivity correlated significantly with tumor degree of differentiation and proliferative activity measured based on Ki67 immunoreactivity. In conclusion, TGF-ß is implicated in the progression of intestinal type of gastric adenocarcinomas and its immunoreactivity assessment for these targets has a prognostic value.

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.