Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors

Robert Emerson, Mingsheng Wang, Lawrence M. Roth, Wenxin Zheng, Fadi W. Abdul-Karim, Fang Liu, Thomas Ulbright, John Eble, Liang Cheng

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Abstract

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.

Original languageEnglish
Pages (from-to)368-374
Number of pages7
JournalInternational Journal of Gynecological Pathology
Volume26
Issue number4
DOIs
StatePublished - Oct 2007

Fingerprint

Sertoli-Leydig Cell Tumor
Leydig Cells
Cellular Structures
X Chromosome Inactivation
Molecular Biology
Sertoli Cells
Neoplasms
Leydig Cell Tumor
Laser Capture Microdissection
Loss of Heterozygosity
Hematoxylin
Eosine Yellowish-(YS)
Paraffin
Formaldehyde

Keywords

  • Loss of heterozygosity
  • Ovary
  • Sertoli-Leydig cell tumor
  • X-chromosome inactivation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Obstetrics and Gynecology

Cite this

@article{d978ff34e4f74854b0d03fdf1e537251,
title = "Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors",
abstract = "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.",
keywords = "Loss of heterozygosity, Ovary, Sertoli-Leydig cell tumor, X-chromosome inactivation",
author = "Robert Emerson and Mingsheng Wang and Roth, {Lawrence M.} and Wenxin Zheng and Abdul-Karim, {Fadi W.} and Fang Liu and Thomas Ulbright and John Eble and Liang Cheng",
year = "2007",
month = "10",
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journal = "International Journal of Gynecological Pathology",
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T1 - Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors

AU - Emerson, Robert

AU - Wang, Mingsheng

AU - Roth, Lawrence M.

AU - Zheng, Wenxin

AU - Abdul-Karim, Fadi W.

AU - Liu, Fang

AU - Ulbright, Thomas

AU - Eble, John

AU - Cheng, Liang

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

KW - Loss of heterozygosity

KW - Ovary

KW - Sertoli-Leydig cell tumor

KW - X-chromosome inactivation

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