Abstract
PurposeThe 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.MethodsFormalin-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.ResultsIn 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.ConclusionThis 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.
Highlights
The estimated 5-year overall survival (OS) for patients with stage IA and IB lung adenocarcinoma (ADC) is 81%–87% and 72%, respectively [1], despite curative-intent surgical resection
cycle progression (CCP) score was an independent significant prognostic marker (P = 0.006) for 5-year lung cancer–specific mortality
On the basis of our and others’ previous publications that demonstrated worse prognosis in patients with micropapillary (MIP) subtype tumors who had undergone limited resection compared with those who had undergone lobectomy [19, 21], we investigated the utility of molecular prognostic score (mPS) in this cohort of patients (Figure 4)
Summary
The estimated 5-year overall survival (OS) for patients with stage IA and IB lung adenocarcinoma (ADC) is 81%–87% and 72%, respectively [1], despite curative-intent surgical resection. Whether adjuvant therapy would improve OS among patients with stage I lung ADC is undetermined. Current National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant therapy for patients with stage IB lung ADC on the basis of tumor size; this follows results from the CALGB 9633 trial [2]. To expand prognostic information beyond tumor size alone, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) proposed a new lung ADC classification in 2011 [9]. A major limitation of this classification is that the majority (40%– 70%) of cases of stage I lung ADC are intermediategrade acinar predominant (ACI) or papillary predominant (PAP) subtypes [11, 13, 14]. Quantitative, reproducible molecular expression signature that is applicable to both stage IA and IB lung ADC tumors and that can be used to further stratify intermediate-grade ADCs, to better identify high-risk patients, would be beneficial
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