Fatty Acid Synthase Overexpression in Testicular Germ Cell Tumors: Potential Role in Progression of Non-Seminomatous Germ Cell Tumors
Kosuke Miyai, Keiichi Iwaya, Osamu Matsubara, Jae Y Ro. National Defense Medical College, Tokorozawa, Saitama, Japan; Methodist Hospital, Houston, TX
Background: Fatty acid synthase (FASN) is a key enzyme for the synthesis of long-chain fatty acid. FASN overexpression is frequently observed in human cancer cells, such as prostate and breast cancer. In addition, elevated FASN pathway has been reported to be implicated in the carcinogenesis of prostate cancer to protect tumor cells from apoptosis (Migita et al. 2009). Testicular germ cell tumors (TGCTs) are classified as seminoma, non-seminomatous germ cell tumor (NSGCT), and their non-invasive precursor lesion, intratubular germ cell neoplasm, unclassified (IGCNU). It is considered that a part of NSGCTs is derived from IGCNU through seminoma, and the rest directly from IGCNU. To our knowledge, there has been no report on the FASN expression status in TGCTs. In this study, we aimed to investigate a role of FASN expression in the progression of TGCTs.
Design: We investigated 50 IGCNUs, 81 seminomas, 28 embryonal carcinomas, 7 choriocarcinomas, 19 yolk sac tumors, and 19 immature teratomas from a cohort of 108 TGCT cases for FASN protein expression by immunohistochemistry. The intensities of FASN immunoreactivity were classified into four categories: no staining (0), weak (1+), moderate (2+), and strong (3+), and the tumor (or tumor component) was defined as FASN overexpression if the tumor showed 2+ or 3+ immunoreactivity.
Results: FASN protein overexpression was observed in 2% (1/50) of IGCNUs, 9% (7/81) of seminomas, 86% (24/28) of embryonal carcinomas, 100% (7/7) of choriocarcinomas, 79% (15/19) of yolk sac tumors, and 39% (7/19) of immature teratomas. In non-tumorous germ cells, FASN overexpression was not detected. There was a significant difference in frequencies of FASN overexpression between each NSGCT component (i.e. embryonal carcinoma, choriocarcinoma, yolk sac tumor, and immature teratoma) and IGCNU (P<0.0001 each) and between each NSGCT component and seminoma (P<0.0001 each).
Conclusions: Overexpression of FASN protein was significantly more frequent in NSGCTs compared with IGCNUs and seminomas, and this finding suggests that it may be implicated in the progression, especially morphological evolution, of NSGCTs.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 170, Wednesday Afternoon