Kawabuchi B, Moriyama S, Hironaka M, Fujii T, Koike M, Moriyama H, Nishimura Y, Mizuno S, Fukayama M
Department of Pathology, Jichi Medical School, Tochigi, Japan.
Int J Cancer. 1999 Feb 19;84(1):49-53. doi: 10.1002/(sici)1097-0215(19990219)84:1<49::aid-ijc10>3.0.co;2-y.
p16, an inhibitor of cell cycle machinery, is frequently inactivated in non-small cell carcinoma of the lung (NSCCL). To clarify the significance of p16 inactivation in the progression of lung adenocarcinoma, we immunohistochemically evaluated p16 protein status and Rb, p53 and cyclin D1 expression in 51 surgically resected adenocarcinomas that were less than 3 cm in diameter (median follow-up period: 52.5 months). Twenty-one of 51 adenocarcinomas showed negative immunostaining for p16. Twenty adenocarcinomas were also negative for Rb, while 31 and 13 were positive for p53 and cyclin D1, respectively. Loss of p16 expression was significantly correlated with scar grade, lymphatic permeation, lymph node metastasis and clinical stage. Rb protein expression was also inversely correlated with scar grade, pleural involvement and vascular invasion. When the cases were stratified according to the expression of both proteins, the Rb-/p16- subset (7/51) consisted of poorly differentiated adenocarcinoma with a higher grade of invasion. While Rb, p53 and cyclin D1 protein status showed no significant correlations with prognosis, p16 inactivation was significantly correlated with poor prognosis, and the prognosis of Rb-/p16- was the worst among the 4 subsets. Inactivation of p16 may play a role in accelerating scar formation and lymph node metastasis, and may contribute through these mechanisms to poor prognosis in patients with small-sized lung adenocarcinoma.
p16是一种细胞周期机制的抑制剂，在非小细胞肺癌（NSCCL）中经常失活。为了阐明p16失活在肺腺癌进展中的意义，我们采用免疫组织化学方法评估了51例直径小于3 cm的手术切除腺癌（中位随访期：52.5个月）中p16蛋白状态以及Rb、p53和细胞周期蛋白D1的表达情况。51例腺癌中有21例p16免疫染色呈阴性。20例腺癌Rb也呈阴性，而p53和细胞周期蛋白D1分别有31例和13例呈阳性。p16表达缺失与瘢痕分级、淋巴管浸润、淋巴结转移及临床分期显著相关。Rb蛋白表达也与瘢痕分级、胸膜受累及血管侵犯呈负相关。根据两种蛋白的表达对病例进行分层时，Rb-/p16-亚组（7/51）由侵袭性较高的低分化腺癌组成。虽然Rb、p53和细胞周期蛋白D1蛋白状态与预后无显著相关性，但p16失活与预后不良显著相关，且Rb-/p16-亚组的预后在4个亚组中最差。p16失活可能在加速瘢痕形成和淋巴结转移中起作用，并可能通过这些机制导致小尺寸肺腺癌患者预后不良。
