Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

// Takashi Eguchi 1, 2 , Kyuichi Kadota 3, 4 , Jamie Chaft 5 , Brent Evans 6 , John Kidd 6 , Kay See Tan 7 , Joe Dycoco 1 , Kathryn Kolquist 6 , Thaylon Davis 6 , Stephanie A. Hamilton 6 , Kraig Yager 6 , Joshua T. Jones 6 , William D. Travis 3 , David R. Jones 1 , Anne-Renee Hartman 6 , Prasad S. Adusumilli 1, 8 1 Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA 2 Division of Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan 3 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4 Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan 5 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA 6 Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA 7 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA 8 Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Prasad S. Adusumilli, email: adusumip@mskcc.org Keywords: molecular prognostic score, CCP score, chemotherapy, adjuvant therapy, overall survival Received: February 08, 2016     Accepted: April 16, 2016     Published: May 2, 2016 ABSTRACT Purpose: The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes. Methods: Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer–specific mortality as the primary outcome. Results: In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer–specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14–2.24; P =0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer–specific mortality (HR=1.77; 95% CI, 1.18–2.66; P =0.006). Five-year lung cancer–specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P <0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer–specific survival ( P <0.001 and 0.015, respectively), compared with low mPS. Conclusion: This study validates CCP score and mPS as independent prognostic markers for lung cancer–specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.