Basement membrane patterns, gelatinase A and tissue inhibitor of metalloproteinase-2 expressions, and stromal fibrosis during the development of peripheral lung adenocarcinoma

To clarify the process and mechanisms of the development and progression of peripheral lung adenocarcinoma, we investigated the relationships among th e patterns of basement membrane (BM), stromal fibrosis, and the expressions of gelatinase A and tissue inhibitor of metalloproteinases-2 (TIMP-2) in 3 3 lesions of atypical alveolar cell hyperplasia (AAH) and 48 lesions of lun g adenocarcinoma, including 24 lesions of bronchioloalveolar carcinoma (BAC ). We found that the architecture of alveolar BM was intact in all 33 AAH l esions and 11 nonsclerosing BAC lesions that formed no central scar, sugges ting that these lesions are early-stage intraepithelial neoplasia. The pree xistent BM of the lung was disrupted, and the BM components around the neop lastic glands were disrupted or absent in the area of the central scar of s ome sclerosing BAC lesions with collapse fibrosis alone (2 of 4) and in tho se of all of the adenocarcinoma lesions associated with desmoplastic stroma l fibrosis (nine sclerosing BAC and 24 non-BAG tumors). These results sugge sted that, in lung adenocarcinomas, destruction of the BM was correlated wi th the formation of a central scar, particularly with desmoplasia. It is li kely that adenocarcinomas with a central scar are advanced and invasive can cers potentially having metastatic activity. The expression of gelatinase A and TIMP-2 was associated with central scar formation as well as with dest ruction of the BM components. Both the neoplastic and stromal cells express ed gelatinase A and TIMP-2 and probably play a role in tumor cell invasion. HUM PATHOL 30:331-338. Copyright (C) 1999 byW.B. Saunders Company.