Biomonitoring environmental stresses in female endometrial carcinoma versus hyperplasia using HSP70 and HER-2/neu proteins

ABSTRACT

The intracellular distribution of heat shock or stress-response proteins [HSP], that are triggered to be induced when a cell undergoes environmental stresses, has presumably protective function to enable cells to increase resistance to the harmful effects of pathogens, heavy metal, heat shock, chemical mutagens or carcinogens. HER-2/neu proto-oncogene is a member of epidermal growth factor receptor or erb gene family that plays a key role in the regulation of normal oncogenic cell growth and has been linked to prognosis and response to therapy. To examine the in vivo environmental stresses in female endometrial carcinoma versus hyperplasia using immunohistochemical staining of HSP70 and HER-2/neu proteins. In the present study, 25 cases of formalin-fixed, paraffin embedded human endometrial tissue sections were examined for the expression of HSP70 and HER-2/neu by immunohistochemistry using a rabbit antihuman HSP70 monoclonal antibody and a rabbit anti-human HER-2/neu polyclonal antibody, respectively. The tissue specimens comprise samples of endometrial hyperplasia and cancers, of which five cases were normal control, four cases were simple hyperplasia, five cases were complex hyperplasia with two cases having atypia, five cases were well differentiated endometrial carcinoma [EC], three cases were moderately differentiated EC, and the last three cases were poorly differentiated EC. Positive staining for HSP70, seen as fine dark brown granules mainly confined to the cytoplasm, was observed in all sections examined. There was marked cellular heterogeneity, ranging from cells completely devoid of staining or with faint staining in poorly differentiated endometrial carcinoma to cells with very intense nuclear and cytoplasmic staining [4+] in normal tissue adjacent to the dysplastic epithelium and in cases of simple endometrial hyperplasia, suggesting a possible protective role of HSP70 in the different stages of carcinogenesis. On the other hand, immunoreactivity for HER-2/neu showed different pattern. Positive strong staining was identified cytoplasmic and/or in cell membrane in poorly, moderately and well differentiated endometrial carcinomas. No immunostaining was observed in normal epithelium and in two cases of simple endometrial hyperplasia. The results suggest that HER-2/neu expression may play a role in the pathogenesis and progression of endometrial carcinoma and together with HSP70 could prove useful biomarkers for diagnosis or disease stratification