Sox2 Protein Expression is an Independent Poor Prognostic... : The American Journal of Surgical Pathology (original) (raw)

Original Articles

Sox2 Protein Expression is an Independent Poor Prognostic Indicator in Stage I Lung Adenocarcinoma

Sholl, Lynette M. MD*; Barletta, Justine A. MD*; Yeap, Beow Y. ScD†; Chirieac, Lucian R. MD*; Hornick, Jason L. MD, PhD*

*Department of Pathology, Brigham and Women's Hospital

†Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Supported in part by Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Lung Cancer 2P50 CA090578-06 (LRC). The authors have no financial disclosures.

Correspondence: Jason L. Hornick, MD, PhD, Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115 (e-mail: [email protected]).

Lucian R. Chirieac, MD and Jason L. Hornick, MD, PhD have contributed equally to the study.

Presented in part at the 99th annual meeting of the United States and Canadian Academy of Pathology (USCAP) in Washington, DC, March 20-26, 2010.

Abstract

Many patients with stage I nonsmall cell lung carcinoma will develop recurrence after surgical excision. Sox2 is a marker of embryonic stem cell pluripotency that is associated with aggressive tumor behavior and is expressed in a subset of lung adenocarcinomas. We hypothesized that Sox2 expression may provide prognostic information in early stage lung adenocarcinomas. We evaluated formalin-fixed, paraffin-embedded tissue from 104 stage I lung adenocarcinomas resected between 1997 and 2000. Sox2 expression was analyzed by immunohistochemistry and compared with clinicopathologic features, time-to-progression, and overall survival (OS). Sox2 expression was detected in 50% of the cases and was more frequent in tumors from older and male patients but not significantly associated with smoking status, tumor stage, grade, or histologic subtype. Compared with Sox2-negative tumors, Sox2 expression predicted a shorter time-to-progression (49% vs. 82% at 5 y; _P_=0.0006) and shorter OS (54% vs. 79% at 5 y; _P_=0.004). By multivariate analysis, Sox2 expression predicted a greater risk of progression among men [hazard ratio (HR) 5.6; 95% confidence interval (CI) 2.3-13.8] and women (HR 2.1; 95% CI 0.8-5.7). Sox2 expression was associated with significantly shorter OS among men (HR 2.5; 95% CI 1.2-5.1), but not in women. Sox2 seems to be an independent predictor of poor outcome in stage I lung adenocarcinomas and may help stratify patients at increased risk for recurrence.