Molecular genetic aberrations of ovarian and uterine carcinosarcomas—a CGH and FISH study

Abstract

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.

Genomic profile of endometrial tumors depends on morphological subtype, not on tamoxifen exposure

“…We did not observe this gain frequently in endometrioid tumors, but it was a recurrent aberration (56%) in the nonendometrioid tumors. Schipf et al (2008) and Schulten et al (2004) also described a frequent gain of 8q in the majority of carcinosarcomas. Furthermore, the frequent gain of 20q (60% of our samples) is in line with the 75% gain in nonendometrioid tumors reported by Schipf et al However, many additional losses were found in our study (Supporting Information Table S2), which were not described by Schipf et al (2008).…”

“…Schipf et al (2008) and Schulten et al (2004) also described a frequent gain of 8q in the majority of carcinosarcomas. Furthermore, the frequent gain of 20q (60% of our samples) is in line with the 75% gain in nonendometrioid tumors reported by Schipf et al However, many additional losses were found in our study (Supporting Information Table S2), which were not described by Schipf et al (2008). This may have technical reasons, like platform use, or may be due to the samples selection (tumor grade, number of tumors studied).…”

Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus: clinicoimmunohistochemical and histogenetic characteristics

“…Carcinosarcoma metastases to other organs most commonly derive from the carcinomatous pattern [3,4,15,18]. It is difficult to explain which factors determine the higher activity of carcinomatous pattern.…”

Seröse Tumoren des Ovars

“…Obwohl diese Tumoren nicht in demselben Umfang analysiert wurden wie die zuvor genannten Entitäten, ist weitgehend klar, dass auf molekularer Ebene viele Gemeinsamkeiten mit dem HGSC bestehen [18]. Die epitheliale Komponente besitzt meistens Charakteristika eines HGSC, zudem wurde eine Assoziation mit einem serösen intraepithelialen Tubenkarzinom beschrieben [4].…”