TY - JOUR
T1 - Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors
AU - Emerson, Robert E.
AU - Wang, Mingsheng
AU - Roth, Lawrence M.
AU - Zheng, Wenxin
AU - Abdul-Karim, Fadi W.
AU - Liu, Fang
AU - Ulbright, Thomas M.
AU - Eble, John N.
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
UR - http://www.scopus.com/inward/record.url?scp=34748854929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34748854929&partnerID=8YFLogxK
U2 - 10.1097/pgp.0b013e31802f3100
DO - 10.1097/pgp.0b013e31802f3100
M3 - Article
C2 - 17885485
AN - SCOPUS:34748854929
SN - 0277-1691
VL - 26
SP - 368
EP - 374
JO - International Journal of Gynecological Pathology
JF - International Journal of Gynecological Pathology
IS - 4
ER -