Extracellular matrix expression in metastasizing and nonmetastasizing adenocarcinomas of the lung

Alterations in extracellular matrix, cell-cell and cell-matrix adhesion, and oncogenes are thought to be important in tumor progression and metastasis. Adenocarcinomas of the lung from 31 patients were studied for immunohistochemical expression of basement membrane molecule type IV collagen, type IV collagenase, and integrins alpha2,3,v adhesion molecules to assess their diagnostic and prognostic importance in pathological stage T2 tumors. The results indicate that with decreasing tumor differentiation, there is a progressive loss of type IV basement membrane collagen (P = .06) and decreased integrin alpha2 expression (P = .03). Type IV collagenase expression was significantly associated with the presence of lymph node metastases, with moderate to strong expression present in 53% T2N1 tumors compared with none (0%) of the T2N0 tumors (P = .008). Integrin alpha(v) was increased in tumors with nodal metastases compared with those without (P = .08). Loss of alpha2 and alpha3 integrins was associated with increased alpha v expression (P = .03). Median survival was 48 months for T2N0 and 20 months for T2N1 (P = .07). In correlating expression of the immunohistochemical markers and survival, type IV collagenase expression was found to be a predictor of survival at a level of P = .07. Measurable alterations in integrins and extracellular matrix, and in particular, expression of matrix-degrading enzyme type IV collagenase may be of prognostic importance in resectable adenocarcinoma of the lung.