Prognostic significance of p27KIP1 expression in resected non-small cell lung cancers: analysis in combination with expressions of p16INK4A, pRB, and p53.

Whether a prognostic role for expression of the tumor suppressor gene (TSG) products exists in resected non-small call lung cancers (NSCLCs) remains controversial. Our study was performed to determine the value of TSGs expressions for patients survival in NSCLCs. We examined 108 resected NSCLCs for the expression of TSG products, p27(KIP1), p16(INK4A), pRB, and p53 that govern cell cycle transition by immunohistochemistry and compared them with patient clinical characteristics and prognoses. Abnormal expressions of p27(KIP1), p16(INK4A), pRB, and p53 were found in 61 (57%), 53 (49%), 42 (39%), and 48 (44%), respectively, of the 108 NSCLCs. Univariate analysis showed abnormal expression of p27(KIP1) to be a strong indicator for poor patient survival, not only in the total cohort (P = 0.0024), but also in subgroups with T1-T2 (P = 0.016), N0 (P = 0.047), and squamous cell carcinomas (P = 0.026), but not according to the expression of p16(INK4A), pRB, or p53. In the Cox regression analysis, p27(KIP1) expression was found to be an independent prognostic factor (P = 0.0148) and associated with pathological stage (P = 0.0278). Our results suggest that abnormal p27(KIP1) expression may be a useful indicator to predict postoperative prognosis, especially in patients with early stage NSCLCs, as compared to other TSG products examined.

Hirabayashi H ，Ohta M ，Tanaka H ，Sakaguchi M ，Fujii Y ，Miyoshi S ，Matsuda H ... -  《JOURNAL OF SURGICAL ONCOLOGY》

Correlation of abnormal RB, p16ink4a, and p53 expression with 3p loss of heterozygosity, other genetic abnormalities, and clinical features in 103 primary non-small cell lung cancers.

Geradts J ，Fong KM ，Zimmerman PV ，Maynard R ，Minna JD ... -  《CLINICAL CANCER RESEARCH》

Prognostic significance of p27KIP1 protein and ki-67 growth fraction in non-small cell lung cancers.

Hommura F ，Dosaka-Akita H ，Mishina T ，Nishi M ，Kojima T ，Hiroumi H ，Ogura S ，Shimizu M ，Katoh H ，Kawakami Y ... -  《CLINICAL CANCER RESEARCH》

Prognostic implications of cell cycle-related proteins in primary resectable pathologic N2 nonsmall cell lung cancer.

Patients who have pathologic N2 (pN2) nonsmall cell lung cancer (pN2 NSCLC) represent a heterogeneous group with regard to prognosis and treatment. Molecular features of NSCLC seem to be of interest. For the current study, to select an appropriate therapeutic strategy for each patient, patients with N2 NSCLC were stratified into homogenous subgroups according to the expression profiles of cell cycle-related markers. The expression levels of retinoblastoma protein (pRb), cyclin D1, p16, p53, and p21 proteins and values of the Ki-67 labeling index were evaluated in 61 primary surgically resected tumor specimens from patients with pN2 NSCLC using immunohistochemistry. The prognostic impact of these markers on overall survival was analyzed in both univariate and multivariate analyses. In univariate analysis, p21, p16, and Ki-67 were correlated significantly with survival. In multivariate analysis, only p21 and p16 influenced survival. Indeed, the group of patients with pN2 NSCLC who were positive for p21 and p16 had the most favorable overall survival (P = .001) and were correlated significantly with the clinical lymph node (cN) status (cN2 disease; P = .008). Moreover, no significant difference in survival was observed between patients with cN0/cN1 disease and patients with cN2 disease within the group (P = .4333). Loss of control of cell-cycle checkpoints is a common occurrence in pN2 NSCLC. Functional cooperation between different cell-cycle regulators constitutes another level of regulation in cell growth control and tumor suppression. Preoperative patients with pN2 NSCLC, even those with cN2 disease, who have positive p21 and p16 protein expression in their primary tumors are expected to have a favorable postoperative prognosis and may be candidates for primary resection.

Mohamed S ，Yasufuku K ，Hiroshima K ，Nakajima T ，Yoshida S ，Suzuki M ，Sekine Y ，Shibuya K ，Iizasa T ，Farouk A ，Fujisawa T ... -  《CANCER》

Cell cycle regulators in bladder cancer: a multivariate survival study with emphasis on p27Kip1.

Korkolopoulou P ，Christodoulou P ，Konstantinidou AE ，Thomas-Tsagli E ，Kapralos P ，Davaris P ... -  《HUMAN PATHOLOGY》