Abstract

Thymic epithelial tumors (TETs) including thymoma (TA) and thymic carcinoma (TC) are rare, and little data are available to guide treatment. As the thymus plays a critical role in immune homeostasis, immunotherapy with checkpoint blockade is an attractive treatment strategy for patients with TET. Published data regarding the expression patterns and prognostic implications of PD-L1 expression in TET have yielded conflicting results, and have included limited data regarding PD-1 expression. A retrospective review was carried out at Ohio State University of 35 pts with TET, with tumor specimens available at our institution from 2000 – 2010. PD-1 and PD-L1 expression was assessed by immunohistochemistry on tumor samples (utilizing PD-1 clone: NAT105 and PD-L1 clone:22C3 antibodies), and graded 0-5 according to expression (0 – no expression, 5 – high expression). Clinicopathologic characteristics assessed included age, grade, stage, overall survival, smoking status, and diagnosis of myasthenia gravis. PD-1 and PD-L1 expression were assessed in 35 pts, including 32 pts with thymoma and 3 pts with thymic carcinoma. PD-L1 expression was detected in 83% (29/35) tumor samples, including 100% (3/3) of thymic carcinoma pts and 81% (26/32) of thymoma pts. PD-1 expression was detected in 77% (27/35) of samples, including 33% (1/3) of thymic carcinoma pts and 81% (26/32) thymoma pts. High levels (IHC >/= 3) of PD-L1 were detected in 57% (20/35) of pts, and high levels of PD-1 expression (IHC >/= 3) were detected in 31% (11/35) pts. A nonsignificant trend towards poorer overall survival was seen in patients with PD-L1 expression (p=0.097, log-rank test). Unlike prior studies, PD-L1 expression was not associated with higher grade tumors (B2, B3, C) or higher stage at diagnosis. Interestingly, high PD-1 expression was significantly associated with lower grade tumors (p = 0.031), but not overall survival. Expression of PD-L1 and PD-1 was not significantly associated with stage at diagnosis, smoking, recurrence, or diagnosis of myasthenia gravis. This study confirms high expression of PD-L1 and PD-1 in TETs, including thymoma and thymic carcinoma. PD-L1 expression was associated with a trend towards shorter overall survival. The high proportion of patients with high PD-L1 and PD-1 expression supports the use of anti PD-1 therapies in this patient population, and prospective trials are needed to assess PD-L1 and PD-1 as predictive and prognostic biomarkers in TET.

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