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

Background. Alpha-1-antichymotrypsin (ACT) is a serine protease inhibitor, expression of which has been shown in various tumor types, but its biologic and clinical implications in tumor tissues are obscure, The authors examined ACT expression in lung adenocarcinoma to determine its clinicopathologic and prognostic significance, Methods, First, reverse transcriptase-polymerase chain reaction (RT-PCR) using oligonucleotide primers specific for ACT and Western blotting and immunohistochemical methods using anti-ACT antibodies were performed in several lung adenocarcinoma cell lines, Secondly, ACT expression in clinical materials was examined immunohistochemically. Results. By RT-PCR, Western blotting, and immunohistochemical methods, ACT synthesis was confirmed in several lung adenocarcinoma cell lines. Seventy-five (52%) of 170 surgically resected lung adenocarcinomas showed positive staining for ACT mainly in the cytoplasm, and the incidence of ACT expression was significantly higher in advanced T classification tumors (P = 0.009) or large sized tumors (P = 0,004). Tumors with a higher rate of mitosis were significantly positive for ACT expression (P = 0.023). Patients with 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 in clinical materials, combined with results of the previous report that ACT in breast cancer acts as a minor growth factor-like substance, suggest that ACT expression in lung adenocarcinoma also may be associated closely with tumor progression and especially with tumor growth. Alpha-l-antichymotrypsin expression status in Stage I tumors may be a potential independent prognostic factor.