ALPHA-1-ANTICHYMOTRYPSIN EXPRESSION IN LUNG ADENOCARCINOMA AND ITS POSSIBLE ASSOCIATION WITH TUMOR PROGRESSION

Background. Alpha-1-antichymotrypsin (ACT) is a serine protease inhibi tor, expression of which has been shown in various tumor types, but it s biologic and clinical implications in tumor tissues are obscure, The authors examined ACT expression in lung adenocarcinoma to determine i ts clinicopathologic and prognostic significance, Methods, First, reve rse transcriptase-polymerase chain reaction (RT-PCR) using oligonucleo tide primers specific for ACT and Western blotting and immunohistochem ical methods using anti-ACT antibodies were performed in several lung adenocarcinoma cell lines, Secondly, ACT expression in clinical materi als was examined immunohistochemically. Results. By RT-PCR, Western bl otting, and immunohistochemical methods, ACT synthesis was confirmed i n several lung adenocarcinoma cell lines. Seventy-five (52%) of 170 su rgically resected lung adenocarcinomas showed positive staining for AC T mainly in the cytoplasm, and the incidence of ACT expression was sig nificantly higher in advanced T classification tumors (P = 0.009) or l arge sized tumors (P = 0,004). Tumors with a higher rate of mitosis we re significantly positive for ACT expression (P = 0.023). Patients wit h ACT-positive adenocarcinoma had a shorter disease free survival (DFS ) and a poor prognosis compared with those who were ACT-negative, most significantly among Stage I tumors (DFS, P = 0.003; overall survival, P = 0.006), In a multivariate analysis, the P value of ACT expression status in Stage I tumors was marginally significant (overall survival , P = 0.058), Conclusions. These results using cell lines suggest the potential productivity of ACT by lung adenocarcinoma cells, The data i n clinical materials, combined with results of the previous report tha t ACT in breast cancer acts as a minor growth factor-like substance, s uggest that ACT expression in lung adenocarcinoma also may be associat ed closely with tumor progression and especially with tumor growth. Al pha-l-antichymotrypsin expression status in Stage I tumors may be a po tential independent prognostic factor.