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Fatty acid synthase overexpression in adult testicular germ cell tumors: potential role in the progression of non-seminomatous germ cell tumors

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Abstract

Overexpression of fatty acid synthase (FASN), which is a key enzyme responsible for the endogenous synthesis of fatty acids, and its association with multistep progression have been demonstrated in various human malignant tumors. We aimed to clarify the potential role of FASN overexpression in the development and progression of adult testicular germ cell tumors (TGCTs). From the primary sites of a cohort of 113 TGCT cases, we obtained 221 histological components: 53 intratubular germ cell neoplasias, unclassified (IGCNUs), 84 seminomas, 32 embryonal carcinomas, seven choriocarcinomas, 21 yolk sac tumors, and 24 teratomas. Samples were analyzed for overexpression of FASN by immunohistochemistry. Intensities of immunoreactivity and the fraction of positive cells were classified into each four categories (intensity, 0 to 3; fraction, 0–10 % = 1, 11–50 % = 2, 51–80 % = 3, and >80 % = 4). The overall score was determined by multiplication of both scores and overall scores greater than 6 were considered FASN overexpression. On a component basis, FASN overexpression was detected in 8 % of seminomas but not in IGCNUs (0 %) and was detected frequently in non-seminomatous germ cell tumors (NSGCTs) (88 % of embryonal carcinomas, all choriocarcinomas, 81 % of yolk sac tumors, and 54 % of teratomas). There were no cases of a mixed tumor (i.e., a tumor with multiple histological components) that overexpressed FASN in seminoma components but not in co-existing NSGCT components, suggesting sequential progression. Our immunohistochemical data suggest that FASN overexpression occurs as a late event during the progression from IGCNUs/seminomas to NSGCTs.

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Acknowledgements

This work was supported in part by a grant-in-aid for Promotion of Defence Medicine from the Ministry of Defense, Japan (KI, HT, OM), and by a grant-in-aid for cancer research from the Ministry of Health, Labor, and Welfare, Japan (HT, KI).

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Basic Pathology, National Defense Medical College, 3-2 Namiki,, Tokorozawa, Saitama, 359-8513, Japan

    Kosuke Miyai, Keiichi Iwaya, Osamu Matsubara & Hitoshi Tsuda

  2. Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

    Seiichi Tamai

  3. Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan

    Tomohiko Asano

  4. Pathology Section, Clinical Laboratory Division, National Cancer Centre Hospital, Tsukiji, Tokyo, Japan

    Hitoshi Tsuda

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  1. Kosuke Miyai
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Correspondence to Kosuke Miyai.

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Miyai, K., Iwaya, K., Asano, T. et al. Fatty acid synthase overexpression in adult testicular germ cell tumors: potential role in the progression of non-seminomatous germ cell tumors. Virchows Arch 464, 221–228 (2014). https://doi.org/10.1007/s00428-013-1525-y

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