The prognostic significance of ATRX in pulmonary carcinoid tumors.

Abstract

e20543 Background: Loss of ATRX, a transcriptional regulator, has been associated with reduced survival in patients with pancreatic neuroendocrine tumors. We aimed to evaluate the prognostic role of ATRX in patients with pulmonary carcinoid tumors in addition to the histological classification. Methods: Resected pulmonary carcinoid tumors and clinical information from 1995 to 2017 were retrospectively identified and recorded. ATRX expression by immunohistochemistry was recorded as percentage of tumor nuclei staining by two pathologists independently. Logistic regression and receiver operating characteristic curve (ROC) were used to establish the cutoff for ATRX expression. Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: 120 patients (38% male) with median age of 59.7 years (range, 14.8-87) were included. The median follow-up was 4.2 years. 52 (43%) patients had atypical carcinoid; 68 (57%) patients had typical carcinoid. 74 (62%) tumors had < 2 mitoses per 10 high-power field. 15 (12%) tumors had necrosis. Loss of ATRX nuclear expression was defined as less than 7.5%, a cutoff identified from ROC curves with area under the curve (AUC) of 0.61. Loss of ATRX nuclear expression was independently associated with atypical pulmonary carcinoid tumor with odds ratio 8.6 (95% CI: 3.0-29, p = 0.0002), after adjusting for lymphovascular invasion and perineural invasion. Although histological classification (atypical vs. typical histology) remains to be the best prognostic predictor for the survival of patients with pulmonary carcinoid tumors, loss of ATRX nuclear expression was also independently associated with shorter disease specific overall survival with hazard ratio 8.6 (95% CI 1.6-46, p = 0.01), after adjusting for tumor necrosis, lymphovascular invasion, and the presence of metastatic disease at diagnosis. Conclusions: Loss of ATRX nuclear expression has significant diagnostic and predictive roles in patients with pulmonary carcinoid tumors in addition to the current histological classification. Further studies on the function of ATRX in the pathogenesis of pulmonary carcinoid tumors and larger outcome studies are needed.