Therapeutic Biomarkers in Thymic Tumors A Clinicopathologic Study from Single Institution
DT Patil, N Dimov, AV Yeldandi, AL deHoyos, N Hou, A Rademaker, MG Blum, JD Patel. Northwestern University, Chicago, IL
Background: Stage and completeness of resection are the best prognostic indicators of thymic tumors. Advanced thymomas are often treated like non small cell lung cancers with cisplatin-based regimens. Excision-repair cross-complementation group 1 (ERCC1), a marker of resistance to cisplatin and its analogues, has not been evaluated in thymic tumors. In this study, we evaluate expression of a panel of markers including ERCC1 for their utility as potential therapeutic targets and correlate their expression with clinicopathological parameters.
Design: Surgical thymic resections (normal-21, hyperplasia-10 and thymomas-31) from 1998-2007 were evaluated for WHO type, size, myasthenia gravis (MG), Masaoka stage and follow-up status. Immunohistochemical expression of HER2/neu, c-kit, EGFR, ERCC1, Octreotide (OCT) and VEGF was evaluated using appropriate controls, scored semiquantitatively & statistically analyzed.
Results: The mean age of patients (15 males, 16 females) was 52 yrs. Subjects with MG (n=8, 45 yrs) were younger than those without MG (n=55 yrs, p=0.06). The tumor distribution per WHO type & Masaoka stage was: A(1), AB(6), B1(7), B2(6), B3(7) and C(4) and Stage I (12), II (7), III (9) and IV (3). Compared to normal/hyperplasia (8%), EGFR was the only biomarker significantly overexpressed in thymomas (92%, p=0.001). In contrast, nuclear ERCC1 expression was higher in normal/hyperplasia (85%/90%) compared to thymomas (A,AB,B -50% and C-100%, p=0.002). In addition, more ERCC1 expression was noted with progressive WHO type (p=0.04) and Masaoka stage (p=0.03). HER2/neu expression was noted in 3 cases (B1, 2 -type C) while only one case was c-kit positive (type C). VEGF was expressed normally in Hassall's corpuscles, all Type C and 80% of other thymomas. OCT expression was higher in thymomas (61%) compared to normal/hyperplasia (39%).
Conclusions: Our findings suggest that anti-EGFR, VEGF and Octreotide agents may be potential therapeutic targets as they are overexpressed in thymomas. Higher expression of ERCC1 in advanced thymomas indicates that cisplatin-based regimens may not be a good treatment option for these patients. EGFR is a good discriminatory marker between normal and abnormal thymic tissue, especially, in small biopsy samples.
Monday, March 9, 2009 1:00 PM
Poster Session II # 215, Monday Afternoon