Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors.
Sertoli-Leydig cell tumors (SLCT) comprise less than 1% of ovarian tumors. The nature of the Leydig cells has been a subject of controversy and it is unclear whether they are clonally related to the neoplasm or instead proliferate as a non-neoplastic response to the Sertoli-cell component. Twelve ovarian SLCT were identified and hematoxylin and eosin and unstained sections were prepared from formalin-fixed, paraffin-embedded tissue blocks. Tissue samples were microdissected from normal tissue, the Sertoli cell component, and the Leydig cell tumor component using the laser capture microdissection method. If present, tissue was also obtained from any heterologous component. Genomic DNA was extracted from the samples and polymerase chain reaction was used to amplify polymorphic sites at 5 loci: D16S402, TP53, IFNA, D17S855, and D11S1318. X-chromosome inactivation (HUMARA) analysis was also performed. LOH and/or nonrandom X-chromosome inactivation was observed in at least 1 of the 6 amplified loci in the Leydig cell component of 10 of the 12 tumors. LOH and nonrandom X-chromosome inactivation patterns of the Sertoli cell component and Leydig cell component were compared. Concordant allelic loss and/or matching X-chromosome inactivation patterns were observed in 8 (67%) of the 12 tumors. In 7 of these tumors similar LOH or X-chromosome inactivation was observed at 1 site. In 1 tumor similar LOH and/or X-chromosome inactivation was observed at 2 sites. Three tumors had heterologous components. The heterologous components similarly shared LOH/X-chromosome inactivation with the Sertoli cell components at 1 site in 1 case and 2 sites in 2 cases. These data suggest that, at least in some cases, the Leydig cell component of SLCT is neoplastic rather than reactive in nature, and shares a common clonal origin with the coexisting Sertoli cell component. Similarly, the heterologous components, when present, appear to share clonal origin with the Sertoli cell components.
Emerson
Robert E
RE
Department of Pathology, Indiana University, Indianapolis, Indiana, USA. reemerso@iupui.edu
Wang
Mingsheng
M
Roth
Lawrence M
LM
Zheng
Wenxin
W
Abdul-Karim
Fadi W
FW
Liu
Fang
F
Ulbright
Thomas M
TM
Eble
John N
JN
Cheng
Liang
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression; D006801:Humans; D007834:Lasers; D007985:Leydig Cells / Q000473:pathology*; D019656:Loss of Heterozygosity; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D018310:Sertoli-Leydig Cell Tumor / Q000235:genetics* / Q000473:pathology*; D049951:X Chromosome Inactivation