PTEN mutations in uterine sarcomas.
OBJECTIVE
Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas.


METHODS
We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis.


RESULTS
Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5).


CONCLUSIONS
These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.
Amant
F
F
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, UZ Gasthuisberg, Leuven, Belgium. Frederic.Amant@uz.kuleuven.ac.be
de la Rey
M
M
Dorfling
C M
CM
van der Walt
L
L
Dreyer
G
G
Dreyer
L
L
Vergote
I
I
Lindeque
B G
BG
Van Rensburg
E J
EJ
D005091:Exons; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007438:Introns; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D012189:Retrospective Studies; D012509:Sarcoma / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human