Expression of p16INK4A and alterations of the 9p21-23 chromosome region in non-small-cell lung carcinomas: Relationship with tumor growth parameters and ploidy status

✍ Scribed by George Mariatos; Vassilis G. Gorgoulis; Panayotis Zacharatos; Athanassios Kotsinas; Thelxiopi Vogiatzi; George Rassidakis; Pericles Foukas; Triantaphyllos Liloglou; Dina Tiniakos; Nikos Angelou; Evangelos N. Manolis; Marinos Veslemes; John K. Field; Christos Kittas

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: French
• Weight: 286 KB
• Volume: 89
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(20000320)89:2<133::aid-ijc6>3.0.co;2-c

✦ Synopsis

The 9p21-23 chromosome region harbors a number of known and putative tumor-suppressor genes (TSGs). The best characterized gene in this area is p16 INK4A (CDKN2A). Alterations of its product have been observed in various malignancies, including non-small-cell lung carcinomas (NSCLCs). We earlier investigated the mechanisms underlying p16 INK4A inactivation. In the present study, we examined, in a series of 87 NSCLCs, its relationship with the kinetic parameters [proliferation index (PI) and apoptotic index (Al)] and the ploidy status of the tumors. In addition, we extended our previous LOH analysis of the 9p21-23 region by examining flanking areas of p16 INK4A . Aberrant p16 expression was observed in 41.4% of the carcinomas. A significant association was found with increased PI (p ‫؍‬ 0.037), but not with apoptosis. Aneuploid tumors were more frequently correlated with abnormal p16 staining (p ‫؍‬ 0.05). A high frequency of allelic imbalance (Alm) was noticed at the D9S161 (51.3%) and D9S157 (64.5%) loci, which lie approximately 4cM centromeric and 7cM telomeric, respectively, to CDKN2A. Abnormal p16 INK4A expression was strongly correlated with Alm at D9S161 (p ‫؍‬ 0.004). Allelic losses at D9S157 occurred more frequently in early stages (p ‫؍‬ 0.018) and were significantly associated with deletions at D9S161 (p ‫؍‬ 0.035). We conclude that, in a sub-set of NSCLCs, (i) abnormal p16 expression contributes to tumor growth mainly by increasing the proliferative activity in the initial stages of carcinogenesis; (ii) the association with aneuploidy merely reflects the impact of aberrant p16 on proliferative activity; and (iii) other putative TSGs possibly reside within the 9p21-23 region that possibly co-operate in certain cases with CDKN2A in the development of NSCLCs.