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Evidence that Leydig cells in Sertoli‐Leydig cell tumors have a reactive rather than a neoplastic profile
Author(s) -
Mooney Eoghan E.,
Man YanGao,
Bratthauer Gary L.,
Tavassoli Fattaneh A.
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19991201)86:11<2312::aid-cncr19>3.0.co;2-6
Subject(s) - leydig cell , leydig cell tumor , biology , pathology , sertoli cell , immunohistochemistry , stroma , polyclonal antibodies , testicle , endocrinology , antibody , luteinizing hormone , medicine , spermatogenesis , hormone , immunology
BACKGROUND Leydig cells are a variable and an inconstant feature of Sertoli‐Leydig cell tumors (SLCT). Controversy exists regarding their neoplastic versus reactive nature, and their molecular biologic profile is unknown. METHODS Six SLCT and one pure Leydig cell tumor were studied. Mitotic counts and immunohistochemistry for Ki‐67 were performed in all cases. Leydig cells, neoplastic tissues, and normal nonneoplastic tissues were microdissected. DNA extracts of these samples were assessed for loss of heterozygosity (LOH) by polymerase chain reaction amplification with ten polymorphic DNA markers that have shown high rates of LOH in a variety of human tumors. Three SLCT and the Leydig cell tumor were assessed for clonality by examining the DNA methylation pattern at a polymorphic site on the androgen receptor gene. RESULTS Leydig cells in SLCT had a low mitotic count (0–1/50 high‐power fields [HPF]) compared with the neoplastic stroma (median, 40/50 HPF). Ki‐67 was positive in < 2% of Leydig cells in all SLCT, compared with a median of 7% in the neoplastic stroma. Clonality analysis confirmed the monoclonality of the neoplastic cells in the Leydig cell tumor. However, the Leydig cells from three SLCT were polyclonal, whereas the monoclonal nature of the neoplastic Sertoli tubules was confirmed in one of these cases and that of mucinous heterologous elements in another case. The Leydig cell tumor showed LOH at four of the eight loci evaluated. Leydig cells from five SLCT were evaluated: one showed LOH at one locus, two showed LOH at two loci, and the remaining two showed no LOH. CONCLUSIONS The demonstration that Leydig cells from SLCT are polyclonal strongly suggests that they are nonneoplastic in nature. This is supported by a low proliferation fraction and a lower fraction of LOH compared with the truly neoplastic Leydig cells. Cancer 1999;86:2312–19. © 1999 American Cancer Society.