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Spermatocytic seminoma (SS) is a rare testicular neoplasm that occurs predominantly in older men. In this study, we aimed to shed light on the histogenesis of SS by investigating the developmental expression of protein markers that identify distinct subpopulations of human spermatogonia in the normal adult testis. We analysed the expression pattern of OCT2, SSX2-4, and SAGE1 in 36 SS cases and four intratubular SS (ISS) as well as a series of normal testis samples throughout development. We describe for the first time two different types of SS characterized by OCT2 or SSX2-4 immunoexpression. These findings are consistent with the mutually exclusive antigenic profile of these markers during different stages of testicular development and in the normal adult testis. OCT2 was expressed predominantly in A(dark) spermatogonia, SSX2-4 was present in A(pale) and B spermatogonia and leptotene spermatocytes, whilst SAGE1 was exclusively present in a subset of post-pubertal germ cells, most likely B spermatogonia. The presence of OCT2 and SSX2-4 in distinct subsets of germ cells implies that these markers represent germ cells at different maturation stages. Analysis of SAGE1 and SSX2-4 in ISS showed spatial differences suggesting ongoing maturation of germ cells during progression of SS tumourigenesis. We conclude that the expression pattern of OCT2, SSX2-4, and SAGE1 supports the origin of SS from spermatogonia and provides new evidence for heterogeneity of this tumour, potentially linked either to the cellular origin of SS or to partial differentiation during tumour progression, including a hitherto unknown OCT2-positive variant of the tumour likely derived from A(dark) spermatogonia.

Original publication

DOI

10.1002/path.2919

Type

Journal article

Journal

J Pathol

Publication Date

08/2011

Volume

224

Pages

473 - 483

Keywords

Adult, Aged, Aged, 80 and over, Antigens, Neoplasm, Biomarkers, Tumor, Child, Preschool, DNA Mutational Analysis, DNA, Neoplasm, Disease Progression, Humans, Infant, Male, Middle Aged, Mutation, Neoplasm Proteins, Organic Cation Transport Proteins, Proto-Oncogene Proteins p21(ras), Receptor, Fibroblast Growth Factor, Type 3, Repressor Proteins, Seminoma, Spermatogonia, Testicular Neoplasms, Testis