Transforming Growth Factor 1 Protein Expression Correlate with Survival in Non-Small Cell Lung Cancer

encodes a cyclin-dependent kinase inhibitor that is transcriptionally activated by the p53 tumor suppressor gene, transforming growth factor 1 (TGF1), AP2, and other pathways. Because p21wafl/ciPl, p53, and TGF11 all regulate apoptosis and the cell cycle, we tested the hypothesis that their relative protein levels would correlate with biological features including the survival of non-small cell lung cancer (NSCLC) patients. We conducted an immunohistochemicab analysis of p2lw i and TGF1 and identified four patient groups with distinct survival outcomes. Concordant p2l ktP) and TGF11 expression (i.e., either high p21wafl/ciPt and high TGF1 expression or low p2lwf )) and bow TGF11 expression) predicted 70% disease-free survival at 2000 days of follow-up. Discordant p2lw il and TGF31 expression (i.e., either high and low TGF11 expression or low and high TGF-f31 expression) predicted 35% disease-free survival (P = 0.0003; log-rank test). These survival relationships were not attributable to differences in grade, stage, or Received 9/26/97; revised 3/23/98: accepted 3/23/98. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with I 8 U.S.C. Section 1734 solely to indicate this fact. I Current address: City of Hope National Medical Center, Duarte, CA 91010. 2 To whom requests for reprints should be addressed, at Laboratory of Human Carcinogenesis, National Cancer Institute, Building 37, Room 2COl, 37 Convent Drive MSC 4255. Bethesda, MD 20892-4255. Phone: (301) 496-2048: Fax: (301) 496-0497: E-mail: [email protected]. p53 status. Although current models do not fully explain these complex interactions, most of these data fit a paradigm whereby TGF-fH regulation determines NSCLC survival. In addition to the survival correlation, we found that high p2l d1 protein expression correlated with high tumor grade (P = 0.014). There is little evidence that p2lw/ protein levels accurately predict p53 mutation status in NSCLC; specifically, 20 of 48 (42%) tumors with p53 mutations contained high levels of p2lwa t protein. These findings indicate that 21wafl/ciPI immunohistochemical analysis may provide useful information concerning the biological properties of NSCLC.