Expression of α6 and β4 integrins in serous ovarian carcinoma correlates with expression of the basement membrane protein laminin

The surface of a normal ovary is covered by a monolayer of epithelial cells that rest on a basement membrane. The glycoprotein laminin is the major noncollagenous protein present in the basement membrane. The integrins α1β1, α2β1, α3β1, α6β1, and α6β4 serve as cell surface receptors for laminin. During the progression of serous ovarian carcinoma, tumor cells are frequently exfoliated from the surface of the ovary, thereby losing contact with the basement membrane. This study was designed to determine whether alterations in integrin expression may be associated with the malignant phenotype of the primary ovarian tumor and exfoliated ovarian carcinoma cells in the ascites fluid. By immunohistochemical staining, the entire surface of epithelial cells of normal ovaries stained positively for β1, α2, and α3 integrins, whereas only the basal surface of the epithelial cells, where they are in contact with laminin, stained positively for α6 and β4. The entire surface of epithelial cells of solid tumors from patients with serous ovarian carcinoma stained positively for β1, α2, and α3 integrins. In most cases, no intact basement membrane surrounded the tumor nests, and staining for α6 and β4 was irregular. When present, the basement membrane stained positively for laminin, and the basal surface of the epithelial cells stained positively for α6 and β4. Ovarian carcinoma ascites cells exhibited a distinct phenotype, with a significant decrease in expression of the α6 and β4 integrin subunits. As α6 and β4 integrin subunits are present at the basal surface of many epithelial cells and serve as receptors for laminin, it is possible that ovarian carcinoma epithelial cells may be released from the basement membrane of the ovary due to their deficit of α6 and β4 integrin subunits.