Does Lung Adenocarcinoma Subtype Predict Patient Survival? A Clinicopathologic Study Based on the New International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification

Introduction: Lung adenocarcinoma is a heterogeneous group of tumors with a highly variable prognosis, not well predicted by the current pathologic classification system. The 2004 World Health Organization classification results in virtually all tumors encountered in clinical practice being allocated to the adenocarcinoma of mixed subtype category. A new classification developed by an international multidisciplinary expert panel sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, is based on histomorphologic subtype and has recently been validated in a North American series of 514 stage I lung adenocarcinomas. We investigated the relationship between the new classification and patient survival in a series of Australian patients with stages I, II, and III lung adenocarcinoma. Methods: We identified 210 patients from a surgical database who underwent resection of lung adenocarcinoma from 1996 to 2009. Two pathologists, blinded to patient outcome, independently performed histopathologic subtyping according to the new classification. Kaplan-Meier curves were used to calculate 5-year survival for each separate histopathologic subtype/variant. Univariate and multivariate analyses were undertaken to control for validated prognostic factors. Results: We confirmed that the new subtypes of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic-predominant adenocarcinoma had a 5-year survival approaching 100%, whereas micropapillary-predominant and solid with mucin-predominant adenocarcinomas were associated with particularly poor survival. Papillary-predominant and acinar-predominant adenocarcinomas had an intermediate prognosis. This effect persisted after controlling for stage. Conclusions: Classification of lung adenocarcinoma according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification correlated with 5-year survival. These relationships persisted after controlling for known prognostic patient and tumor characteristics. The new classification has advantages not only for individual patient care but also for better selection and stratification for clinical trials and molecular studies.