Sox2 Protein Expression Is an Independent Poor Prognostic Indicator in Stage I Lung Adenocarcinomas
LM Sholl, JA Barletta, LR Chirieac, JL Hornick. Brigham and Women's Hospital, Boston
Background: Despite surgical excision, 40% of patients with stage I non-small cell lung carcinoma will recur. Histologic parameters such as tumor subtype, grade, and the presence of lymphovascular invasion are inconsistent predictors of outcome. Prognostic immunohistochemical markers may help to identify patients at high risk of recurrence. Sox2 is a marker of embryonic stem cell pluripotency that has been associated with aggressive tumor behavior and is expressed in some germ cell tumors, lung and esophageal squamous cell carcinomas, and a subset of lung adenocarcinomas. We hypothesized that Sox2 expression may provide prognostic information in early stage lung adenocarcinomas.
Design: Formalin-fixed paraffin embedded lung adenocarcinomas were retrieved from the surgical pathology files. We evaluated a test cohort of 62 lung adenocarcinomas resected between 1997 and 1999, including 37 stage I tumors, and a validation cohort of 67 stage I lung adenocarcinomas resected in 2000. Sox2 expression was analyzed by immunohistochemistry and compared to clinicopathologic features and time to progression (TTP), defined as the interval between date of surgery and clinical or radiographic progression.
Results: In the test and validation cohorts, respectively, males comprised 35 and 44%, median age was 70 and 65 years, smokers comprised 78 and 81%, and lobectomy (versus wedge resection) was performed in 68 and 60%. Overall, 75% of adenocarcinomas were mixed subtype; acinar was the most common predominant pattern. Sox2 expression was detected in 40% of the test cohort and 52% of the validation cohort. Sox2 expression was not associated with age, gender, smoking status, tumor stage (Ia vs Ib), grade, or histologic subtype. Survival analysis showed that patients with stage I adenocarcinoma with Sox2 expression had a shorter TTP than those without expression (n=17, HR=7.3, P=0.005 in the test cohort; n=35; HR=2.7, P=0.02 in the validation cohort). By multivariate analysis, Sox2 independently predicted a shorter TTP in both the test and validation cohorts (P=0.02 and P=0.003, respectively).
Conclusions: In this study we show that Sox2 is expressed in approximately half of stage I lung adenocarcinomas and is an independent predictor of poor outcome, and we confirm the findings in an independent validation dataset. Sox2 expression can help stratify patients with stage I adenocarcinoma who have an increased risk of recurrence.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 251, Tuesday Morning