Alterations of expression of Rb, p16(INK4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance

Inactivation of the Rb pathway in non-small cell lung carcinoma (NSCLC) occ urs mostly through inactivation of the cyclin-dependent kinase inhibitor p1 6(INK4A) and/or up-regulation of cyclin D1, In order to assess the frequenc y and the prognostic value of these abnormalities in NSCLC, immunohistochem ical analysis of Rb, p16(INK4), and cyclin D1 has been performed on 168 cas es of NSCLC including 77 squamous cell carcinomas, 43 adenocarcinomas, and 48 basaloid carcinomas, The reduced survival rate of basaloid carcinoma (st age I-II) compared with other histological types of NSCLC was confirmed (p= 0.008). Loss of protein expression of Rb and p16(INK4A) was observed in 12 per cent and 58 per cent of NSCLC cases respectively and cyclin D1 overexpr ession in 43 per cent. There was an inverse correlation between Rb and p16 expression (p<0.0001) and a direct correlation between Rb and cyclin D1 exp ression (p=0.0007). in univariate analysis, Rb-negative adenocarcinomas at stages I-II had a significantly shorter survival than Rb-positive cases (p= 0.04) and stages I-II p16-positive cases had a shorter survival than p16-ne gative cases (p=0.02), which was more significant in basaloid carcinoma (p= 0.003). p16 status retained its influence on survival in multivariate analy sis at stage I-II for all cases (p=0.01) and for basaloid carcinoma (p=0.00 5). Cyclin D1 overexpression did not influence survival. Combined Rb/p16/cy clin D1 phenotypes in univariate analysis showed a shorter survival for Rb- negative/p16-positive/cyclin D1-negative tumours (p=0.002). These results, linked to previous data, indicate that the Rb pathway of G1 arrest is initi ally disrupted in the vast majority of NSCLCs (83 per cent), but could not confirm an unfavourable role for each individual event (p16(INK4A) loss or cyclin D1 up-regulation) in prognosis. Copyright (C) 1999 John Wiley & Sons , Ltd.