Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size. An immunohistochemical analysis of 102 cases.

Abstract

Laminin-5 plays an important role in cell migration during tissue remodeling and tumor invasion. The authors studied the expression of laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension < or = 2 cm) using a monoclonal antibody against the laminin gamma2 chain, and they also investigated the associations of laminin-5 with clinicopathologic characteristics. Prognostic significance of increased laminin-5 expression was evaluated using the Kaplan-Meier method and the Cox proportional hazard model. Overall, laminin-5 expression was observed in 82 cases (80.4%): 7 of 18 (38.9%) bronchioloalveolar carcinomas and 75 of 84 (89.3%) invasive adenocarcinomas. Laminin-5 was preferentially localized in the cytoplasm of tumor cells at the tumor-stromal interface, where budding or dissociation of cancer cells was frequently observed. Overexpression of laminin-5 (24 cases, 23.5%) was associated with vascular invasion (P = 0.021) and stromal fibroblastic reaction (P = 0.005) but not with nodal involvement, lymphatic invasion, or pleural invasion. Survival analysis revealed that overexpression of laminin-5 was associated with shorter patient survival (P = 0.0027 by log rank test). On multivariate analysis, overexpression of laminin-5 was an independent prognostic factor (P = 0.030), as were nodal involvement (P < 0.0001), vascular invasion (P = 0.047), and lymphatic invasion (P = 0.0047) in a whole cohort of patients. Moreover, when patients with Stage I (International Union Against Cancer [UICC] staging system) disease were considered in multivariate analysis, overexpression of laminin-5 was the only significant prognostic factor (P = 0.022), whereas vascular invasion had a marginally significant impact (P = 0.07) on patient survival. The authors' results showed that laminin-5 is frequently expressed by cancer cells at the invasive front of lung adenocarcinoma. The study concluded that overexpression of laminin-5 may be a useful prognostic factor in patients with small-sized lung adenocarcinoma, especially in Stage I cases.