Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma.
BACKGROUND
The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality.


METHODS
Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome.


RESULTS
The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12-1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10).


CONCLUSIONS
This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality.
*Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; †Myriad Genetics, Inc., Salt Lake City, UT; ‡Myriad Genetic Laboratories, Inc., Salt Lake City, UT, §Levine Cancer Institute, Charlotte, NC, ‖Istituto Europeo di Oncologia, Milan, Italy; ¶Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX; #Royal Infirmary of Edinburgh, Edinburgh, Scotland; and **School of Medicine, University of St. Andrews, St. Andrews, Scotland.
Raphael
R
Bueno
Elisha
E
Hughes
Susanne
S
Wagner
Alexander S
AS
Gutin
Jerry S
JS
Lanchbury
Yifan
Y
Zheng
Michael A
MA
Archer
Corinne
C
Gustafson
Joshua T
JT
Jones
Kristen
K
Rushton
Jennifer
J
Saam
Edward
E
Kim
Massimo
M
Barberis
Ignacio
I
Wistuba
Richard J
RJ
Wenstrup
William A
WA
Wallace
Anne-Renee
AR
Hartman
David J
DJ
Harrison
D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D005260:Female; D005557:Formaldehyde; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology*; D008297:Male; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D016707:Tissue Fixation
D005557:Formaldehyde