PURPOSE: Akt is a signal transduction protein that plays a central role in inhibiting apoptosis in a variety of cell types including human cancer cells. In cell lines derived from human non-small cell lung cancers (NSCLCs), Akt has been shown to confer chemoresistance by inhibition of apoptosis in response to different chemotherapeutic agents including platinum-based agents, which are often the first-line therapy for NSCLCs. Only 20% to 30% of patients with NSCLC treated with chemotherapy have clinical evidence of response. The purpose of this study is to determine whether or not overexpression of activated Akt [i.e., phosphorylated Akt (pAkt)] is correlated with survival. EXPERIMENTAL DESIGN: We studied tumors from 61 patients with NSCLC in three tissue microarrays. All patients were followed for a period of 10 years or until death. The arrays were studied immunohistochemically with antibodies against pAkt, p53, and Ki-67. RESULTS: There was a statistically significant difference in survival between the 14 patients with strong pAkt staining and the 47 patients with weak to absent pAkt staining both by log-rank (P = 0.0416) and Breslow analysis (P = 0.0446). Difference in survival time with respect to pAkt status was also statistically significant even after accounting for stage at diagnosis (P = 0.004). Neither p53 nor Ki-67 was a statistically significant prognostic factor. CONCLUSIONS: Overexpression of pAkt is an independent prognostic factor. Additional studies of human NSCLCs are warranted to drive the development of targeted tumor-specific antineoplastic therapies.
PURPOSE:Akt is a signal transduction protein that plays a central role in inhibiting apoptosis in a variety of cell types including humancancer cells. In cell lines derived from human non-small cell lung cancers (NSCLCs), Akt has been shown to confer chemoresistance by inhibition of apoptosis in response to different chemotherapeutic agents including platinum-based agents, which are often the first-line therapy for NSCLCs. Only 20% to 30% of patients with NSCLC treated with chemotherapy have clinical evidence of response. The purpose of this study is to determine whether or not overexpression of activated Akt [i.e., phosphorylated Akt (pAkt)] is correlated with survival. EXPERIMENTAL DESIGN: We studied tumors from 61 patients with NSCLC in three tissue microarrays. All patients were followed for a period of 10 years or until death. The arrays were studied immunohistochemically with antibodies against pAkt, p53, and Ki-67. RESULTS: There was a statistically significant difference in survival between the 14 patients with strong pAkt staining and the 47 patients with weak to absent pAkt staining both by log-rank (P = 0.0416) and Breslow analysis (P = 0.0446). Difference in survival time with respect to pAkt status was also statistically significant even after accounting for stage at diagnosis (P = 0.004). Neither p53 nor Ki-67 was a statistically significant prognostic factor. CONCLUSIONS: Overexpression of pAkt is an independent prognostic factor. Additional studies of human NSCLCs are warranted to drive the development of targeted tumor-specific antineoplastic therapies.
Authors: Marie Cumberbatch; Ximing Tang; Garry Beran; Sonia Eckersley; Xin Wang; Rebecca P A Ellston; Simon Dearden; Sabina Cosulich; Paul D Smith; Carmen Behrens; Edward S Kim; Xinying Su; Shuqiong Fan; Neil Gray; David P Blowers; Ignacio I Wistuba; Chris Womack Journal: Clin Cancer Res Date: 2013-11-27 Impact factor: 12.531
Authors: Akihiko Yoshizawa; Junya Fukuoka; Shigeki Shimizu; Konstantin Shilo; Teri J Franks; Stephen M Hewitt; Takeshi Fujii; Carlos Cordon-Cardo; Jin Jen; William D Travis Journal: Clin Cancer Res Date: 2009-12-15 Impact factor: 12.531