Expression of surfactant-associated protein in non-small-cell lung cancer: a discriminant between biologic subsets

We examined expression of the major surfactant-associated protein SP-A, a product characteristic of type II pneumocytes, in a panel of 126 non-small-cell lung carcinomas (NSCLC) by immunohistochemistry using routine paraffin-embedded material. In nonneoplastic lung, the expression was seen in normal and reactive type II pneumocytes. Based on a defined staining index composed of the number of cells and the staining intensity, 32% of all the NSCLC revealed SP-A immunoreactivity that was mostly focal. The highest incidence (50%) was demonstrated in adenocarcinomas having papillolepidic growth patterns (which include the bronchioloalveolar and papillary subtypes), followed by other subtypes of adenocarcinomas (31%) and other types of NSCLC (14%). Patients with SP-A expressing tumors had male/female ratio 1.1, as compared to 2.2 in all NSCLC or 2.0 in papillolepidic tumors. SP-A immunoreactivity in tumors was associated with lighter smoking history, significantly so in men (P2 = .016). The finding of a marker characteristic of peripheral, alveolar cell differentiation in all adenocarcinomas is of interest and supports the concept of common pathogenesis for adenocarcinomas. We conclude that SP-A expression occurs predominantly, but not exclusively, in adenocarcinomas, particularly in those with papillolepidic growth pattern. SP-A expression may delineate biologically and clinically interesting subsets of NSCLC.