p16 inactivation in small-sized lung adenocarcinoma: Its association with poor prognosis

p16, an inhibitor of cell cycle machinery, is frequently inactivated in non -small cell carcinoma of the lung (NSCCL). To clarify the significance of p 16 inactivation in the progression of lung adenocarcinoma, we immunohistoch emically evaluated p16 protein status and Rb, p53 and cyclin D1 expression in 51 surgically resected adenocarcinomas that were less than 3 cm in diame ter (median follow-up period: 52.5 months). Twenty-one of 51 adenocarcinoma s showed negative immunostaining for p16. Twenty adenocarcinomas were also negative for Rb, while 31 and 13 were positive for p53 and cyclin D1, respe ctively. Loss of p16 expression was significantly correlated with scar grad e, lymphatic permeation, lymph node metastasis and clinical stage. Rb prote in expression was also inversely correlated with scar grade, pleural involv ement and vascular invasion. When the cases were stratified according to th e expression of both proteins, the Rb-/p16- subset (7/51) consisted of poor ly differentiated adenocarcinoma with a higher grade of invasion. While ph, p53 and cyclin DI protein status showed no significant correlations with p rognosis, p16 inactivation was significantly correlated with poor prognosis , and the prognosis of Rb-/p16- was the worst among the 4 subsets. Inactiva tion of p16 may play a role in accelerating scar formation and lymph node m etastasis, and may contribute through these mechanisms to poor prognosis in patients with small-sized lung adenocarcinoma. (C) 1999 Wiley-Liss, Inc.