Growth pattern correlates with the distribution of basement membrane and prognosis in lung adenocarcinoma

Lung adenocarcinoma frequently has a histologic heterogeneity, particularly with regard to its cell morphology and growth pattern, with or without stromal desmoplasia. However, little is known about the relationship between morphologic heterogeneity and the destruction of BM. We selected 147 foci showing different growth patterns studied in 76 patients with lung adenocarcinoma and examined immunohistochemically the distribution of BM antigens, as well as the expression of MMPs and TIMP-2. BM antigens were more highly preserved in foci of the BAC growth pattern (94.7%) than in those of the papillary/acinar (24.5%) and solid patterns (16.1%) (p<0.01). MMP-2-positive cancer cells were significantly more frequent in poorly preserved foci of BM antigens than in preserved foci (p<0.05). The population of TIMP-2-positive cancer cells showed a positive correlation with BM preservation (p<0.05). However, no significant relationship between growth pattern and expression of MMP-9 and -14 was found. BM antigens had almost totally disappeared in desmoplastic foci. Multivariate analyses revealed that pathologic stage and high expression of TIMP-2 were independent prognostic factors. These findings indicate that the histologic heterogeneity of lung adenocarcinomas is partly related to the cancer cell-stromal interaction, in particular through BM preservation or destruction, which was mainly affected by cancer cell expression of MMP-2 and TIMP-2 in lung adenocarcinomas.