Immunohistochemical expression of TGF-beta1, p21WAF1, p53, Ki67, and angiogenesis in gastric carcinomas: a clinicopathologic study

Abstract

Background: Transforming growth factors-beta (TGF-betas) are multifunctional polypeptides with crucial role as regulators of cellular growth and differentiation. It has been reported that TGF-beta1 plays a biphasic action on tumorigenesis thus inducing or inhibiting malignant properties of the epithelial cells.

Methods: TGF-beta1 expression was analyzed in 56 patients with gastric carcinoma by immunohistochemical methods and compared with the expression of p21, p53, and Ki67, as well as with angiogenesis. The correlation of these markers with clinicopathological parameters was also evaluated.

Results: TGF-beta1 expression was detected in 71% of tumors and was more frequent in adenocarcinomas of the intestinal type (p < 0.001). Positivity of p21WAF1, and p53 was observed in 32% and 51% of the tumors, respectively. A high Ki67 proliferating index was detected in 53.5% of the tumors. TGF-beta1 expression was significantly correlated with p21 expression (p < 0.001) and was inversely correlated with microvessel density. p21 expression was also higher in tumors with low proliferating index (p < 0.01). There was no apparent correlation between the expression of these markers and tumor stage, depth of invasion, or lymphnode metastases.

Conclusion: The findings show that TGF-beta1 may be involved in the activation of the cdk inhibitor p21WAF1 in gastric adenocarcinomas, suggesting p53-independent induction of p21 in gastric cells. TGF-beta1 does not seem to contribute to the alteration of the angiogenic status of these tumors.