Expression of SOX2 and p63 Do Not Have Independent Prognostic Significance in Stage I Lung Adenocarcinoma.
Alexandra E Kovach, Eugene J Mark, Mari Mino-Kenudson. Massachusetts General Hospital, Boston
Background: A myriad of proposed revisions to the classification of lung adenocarcinoma have attempted to tighten the correlation between histology and prognosis, and supplementation of histology by immunohistochemical and molecular markers may prove necessary. The SOX2 oncogenic transcription factor is expressed in lung squamous cell carcinomas and a subset of lung adenocarcinomas; its overexpression has recently been reported to be a prognostic marker for stage I adenocarcinomas. p63 also may be expressed in lung adenocarcinomas in a patchy manner; the significance of this is unclear. We sought to evaluate SOX2 and p63 expression in a cohort of stage I lung adenocarcinomas in the context of histologic subtype and clinical outcome.
Design: Lung adenocarcinomas resected at MGH between 2000 and 2004 were reviewed. Tissue microarrays were constructed from multiple sections in each of 104 cases. SOX2 and p63 expression were assessed by immunohistochemistry and compared to clinicopathologic features and disease free survival (DFS). For each antibody, nuclear expression in > 5% of tumor cells was considered positive.
Results: The cohort consisted of 59 women and 45 men, with an average age of 68 yrs (SD 9 yrs). The majority of cases (82, 78%) were of mixed histologic subtype, with acinar subtype being the most common predominant pattern (42, 40%). SOX2 expression was seen in 83 (80%) cases and p63 expression in 19 (18%). Of the p63 positive cases, 15 (80%) were also positive for SOX2. There was no significant association between the expression of SOX2 or p63 and predominant histologic subtype; however, p63 tended to be overexpressed in BAC components. Expression of both proteins was also not associated with age, gender, tumor stage (Ia vs. Ib), or tumor grade. Survival analysis showed that patients with stage I adenocarcinoma with SOX2 expression had a slightly shorter DFS than those without (5 year DFS rate: 68% vs. 84%), but the difference did not reach statistical significance (log-rank p=0.2788). There was no difference in outcomes between tumors with p63 overexpression and those without.
Conclusions: SOX2 and p63 do not have independent prognostic significance in stage I lung adenocarcinomas in this study. The prevalence of SOX2 expression in stage I lung adenocarcinomas in our cohort was much higher than that previously reported. Differences in populations, different lots of antibodies used, and/or thresholds of observers for positive expression must be considered when evaluating outcome results as studied here.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 254, Tuesday Afternoon