Alteration of
integrin expression in a number of different malignant diseases has been recognized, with a trend of downregulation of
collagen-
laminin binding
integrin expression in epithelial
tumor types noted. This study evaluated the expression of a panel of
integrin subunits that included subunits that form receptors that bind to
collagen and
laminin (alpha 2, alpha 3, alpha 6 beta 4) and subunits that form receptors that bind to
fibronectin and
fibrinogen (alpha 5, alpha V, beta 3, beta 6) in 51 specimens of non-
small cell carcinoma (NSCCA) of the lung by use of immunohistochemistry.
Integrin expression was then correlated with histologic type (squamous vs.
adenocarcinoma), absence or presence of hilar or mediastinal nodal
metastasis at resection, and cellular differentiation (well or poorly differentiated). In general, downregulation of the
collagen-
laminin binding subunits was noted in
tumor cells of the NSCCA specimens when compared to the progenitor normal bronchial epithelium. No differences were noted in
integrin expression between squamous cell and
adenocarcinoma or between node-positive or node-negative
tumors. However, downregulation of the
integrin subunit alpha 3 was noted to be significantly more common in poorly differentiated
tumors (p = 0.02) and several of the other
collagen-
laminin binding subunits also appeared to be more downregulated in poorly differentiated
tumors. No upregulation was seen in the alpha 5 subunit of the
fibronectin receptor or the beta 3 subunit of the
vitronectin receptor, however, approximately 50% of
tumors showed upregulation of the beta 6 subunit, the great majority of these being well-differentiated, node-negative
tumors. Downregulation of the
collagen-
laminin integrins may thus be associated with differentiation of NSCCA, but not
metastasis, and may serve as an adjunctive prognostic marker of disease. The beta 6 subunit appears to be associated with malignant transformation, but may serve as a positive prognostic factor.