Differential expression of basement membrane type IV collagen α chains in gastric intramucosal neoplastic lesions

Background. The histological diagnosis of gastric intramucosal neoplastic lesions (GINLs) is controversial among experienced pathologists. Although the destruction of the epithelial basement membrane (BM) and the invasion of neoplastic epithelial cells into the interstitium of the lamina propria is distinct proof of "intramucosal carcinoma," histological evaluation of GINLs is difficult and ambiguous, especially intestinal-type adenocarcinoma. Type IV collagen is a major component of the BM, and comprises six genetically distinct alpha(IV) chains, alpha 1(IV) to alpha 6(IV). In several types of carcinomas, the loss of alpha 5/alpha 6(IV) chains of the epithelial BM at an early invasive stage has been reported. However, the expression of alpha 5/alpha 6(IV) chains in GINLs is still unclear. We examined the immunohistochemical expression of alpha(IV) chains in GINLs and investigated whether the expression pattern was a diagnostic marker of gastric intramucosal carcinoma. Methods. The expression of alpha(IV) chains and Ki-67 in 60 resected GINL specimens was immunohistochemically examined. Results. In normal gastric epithelium, alpha 1(IV), alpha 2(IV), alpha 5(IV), and alpha 6(IV) chains were expressed continuously in the BM. In most tubular adenomas (Japanese classification), these four chains were stained continuously in the BM, whereas in tubular adenocarcinomas (Japanese classification), the alpha 5/alpha 6(IV) chains had disappeared, partially or completely. The expression of alpha 5/alpha 6(IV) chains was closely related to the grade of histological atypia. In addition, the loss of alpha 5/alpha 6(IV) chains was significantly correlated with tumor cell growth activity. Conclusions. The loss of alpha 5/alpha 6(IV) chains might be a useful diagnostic finding for gastric intramucosal carcinoma in GINL cases.