HER-2/neu and E-cadherin Expression and Microsatellite Instability in Gastric Dysplasia

BACKGROUND Gastric dysplasia (GD) is a precursor lesion of gastric adenocarcinoma. Intestinal type gastric carcinoma commonly shows microsatellite instability (MSI) and the diffuse type is associated with down regulation of E-cadherin. HER-2/neu is over-expressed in some cases of gastric cancer. In this study, MSI and expression rates of HER-2/neu and E-cadherin in GD were evaluated. METHODS Paraffin blocks of 21 cases of low grade dysplasia (LD), 11 cases of high grade dysplasia (HD) and 25 cases of indefinite for dysplasia (ID) were collected. After deparaffinization and antigen retrieval, the sections were incubated with antibodies against E-cadherin, hMLH1, hMSH2 and HER-2/neu. The streptavidin-biotin complex method was used followed by peroxidase enzyme development with diaminobenzidine. RESULTS HER-2/neu was positive in six cases of HD (50%), four LD (21%) and two ID (9%). E-cadherin was absent in two cases of LD and showed normal expression in all HD and ID cases. hMLH1 expression was absent or markedly decreased only in the zones of dysplasia in HD (3/11), LD (3/21) and ID (4/25). Absence or diminished expression of hMSH2 was seen in HD (3/11), LD (2/21) and ID (3/25) cases. HER-2/neu expression showed close association with diminished expression of hMLH1 or hMSH2 (p < 0.05). CONCLUSION Stepwise increase in the expression rate of HER-2/neu was seen in ID, LD and HD cases implying its role in cancer evolution. The absence of hMLH1 and hMSH2 in GD may predispose individuals to over-expression of other oncogenes such as HER-2/neu. Abnormal expression of E-cadherin is not a frequent finding in GD.