Aberrant Expression of pRb and p16INK4A Proteins in Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Their Relationship with Patient Survival: A Retrospective Cohort Study
CC Huang, M Leon, C Elkins, CJ Yao, Y Li, K Gibson, G He, G Otterson, M Villalona, Y Tang, WQ Zhao. Ohio State Unversity Medical Center, Columbus, OH; South Center University, The 3rd Xiang-Ya Medical School, Changsha, Hunan, China; Ohio State University Medical Center, Columbus, OH
Background: Deregulation of several genes involved in cell cycle control has been reported in Non-Small cell lung cancer (NSCLC). The protein expression of p16INK4A, pRb, p53 and the copy number alterations of CDKN2A gene in NSCLC and their association with patients' survival were investigated.
Design: 73 NSCLC (M:43, F:30) (median age=65.5) at stage IA to IIB were enlisted in this study. A TMA was built on the FFPE tissues. The IHC for p16INK4A, pRb, and p53 were performed and scored as negative (0), low (1+), and high (2+ and 3+). The FISH for CDKN2N(p16) gene was performed on the TMA and/or on FFPE tissues. The ratio of gene copy numbers (CPN) to centromere (CEP9) was calculated. The CPN were expressed as normal (ratio of 1), heterozygous loss (0.5), hemizygous loss (0), polysomy (>6 copies but ratio<2), and amplification (>2.1). The five-year absolute survival rate after the diagnosis was used.
Results: The majority of cases were adenocarcinoma (69.9%). p16INK4A protein was correlated significantly with CPN of p16 (p=0.0007). Higher p16INK4A expression was observed in 30% cases. Overexpression of p16INK4A with either p16 amplification or polysomy was associated with a poor prognosis (OR 7.519, 95% CI 1.106-15.521, p=0.009). In cases with negative p16INK4A IHC, 74.5% cases had a normal CPN, and were not correlated with survival (p>0.05). However, among those p16INK4A negative cases, the lower pRb expression was associated with a longer survival (86%, 24/28) which was significantly different from those with a shorter survival (30%, 7/23) (p<0.0001). Furthermore, without considering p16INK4A status, overexpression or no expression of pRb made up to 60% and 27.5%, respectively, of the patients with a shorter survival (n=40); which was significantly higher than those with longer survival in which only 16.7% and 6.7% (p<0.001) had over- or none expression. Therefore, the pRb expression alteration was an independent predictor for poor survival.
Conclusions: The overexpression of p16INK4A with either CDKN2N(p16)amplification or polysomy was associated with a poor prognosis. Higher pRb expression in p16INK4A negative NSCLC cases was also associated poor prognosis.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 252, Monday Morning