Molecular genetic aberrations of ovarian and uterine carcinosarcomas--a CGH and FISH study.
The origin of carcinosarcomas of the ovary and uterus has long been discussed. In this study, we used a molecular-genetic approach to elucidate the tumorigenesis of carcinosarcomas of these organs correlating our findings with the specific biphasic pattern of these tumors. We analyzed a series of 30 paraffin-embedded carcinosarcomas of the ovary and the uterus using comparative genomic hybridization (CGH) and fluorescence in-situ hybridization (FISH). In general, gains (85%) were observed more frequently, than losses (30%). Characteristic and frequent chromosomal amplification was observed on chromosome 8q and 20q (42 and 70%). FISH revealed c-myc (8q24.12) and ZNF217 (20q13.2) amplification in 78 and 87%. Amplification of ZNF217 was mostly seen in both tumor components, whereas amplification of c-myc was observed less often in the sarcomatous than in the carcinomatous tumor component. Analysis of the proliferation index using Ki67 immunohistochemistry revealed a strong or moderate expression in all cases, wherein the carcinomatous tumor component showed significantly a higher proliferation index compared to the sarcomatous tumor areas. Although our results are in agreement with a monoclonal origin of ovarian and uterine carcinosarcomas, the carcinomatous component seems to be the more aggressive part of the tumor. Furthermore, the observed patterns of genetic aberrations are highly similar to those of serous carcinomas. This is compatible with the current opinion that these neoplasms should be considered as metaplastic carcinomas.
Schipf
Alexander
A
Institute of Pathology, KSL Luzern, 6000 Luzern 16, Switzerland. alexander.schipf@ksl.ch
Mayr
Doris
D
Kirchner
Thomas
T
Diebold
Joachim
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002296:Carcinosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002869:Chromosome Aberrations; D005260:Female; D020570:Genes, myb / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization / Q000379:methods*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D015534:Trans-Activators; C113698:ZNF217 protein, human