Molecular Alterations in Endometrial Carcinosarcomas (ECS).
Michele Biscuola, Koen Van De Vijver, Maria Angeles Castilla, Laura Romero-Perez, Maria Angeles Lopez-Garcia, Jose Palacios, Esther Oliva. Hospital Universitario Virgen del Rocío-IBIS (Instituto de Biomedicina de Sevilla), Seville, Spain; Massachusetts General Hospital, Boston
Background: Carcinosarcomas (CS) are uncommon but aggressive neoplasias with biphasic histology of carcinomatous and sarcomatous elements. Although they develop in different organs, they are most common in the endometrium, breast, lung, kidney and upper aerodigestive tract. Due to the relative rarity of Endometrial Carcinosarcomas (ECS) the pathogenesis and the specific genetic alterations underlying these tumors are still not well known.
Design: Samples from 76 ECS were obtained from the Pathology Department Massachusetts General Hospital (Boston, MA, USA). Representative areas were carefully selected from the H&E-stained sections of each tumour and two tissue cores were obtained from each specimen. Immunohistochemistry was carried out on TMA sections by the Envision method (Dako, CA, USA) using the following antibodies: TP53, p16, EGFR and β-Catenin. Fluorescence in Situ Hibridization was performed on TMA sections with Abbott Molecular Probes for EGFR. DNA was isolated from punches of the selected areas. Sequence analysis of the Exon 3 of the CTNNB1 gene was performed on those samples that shown positive nuclear staining for β-Catenin antibody. Aliquots of 41 DNA samples were sent to SEQUENOM® GMBH. SEQUENOM®'s OncoCartaTM Panel is a set of pre-designed and pre-validated SNP assays. It offers analysis of 238 simple and complex mutations across 19 common oncogenes (AKT-1, BRAF, EGFR, KIT, MET, PDGFRα, PIK3CA, H-RAS, K-RAS, N-RAS among others). Data analysis was performed with the MassARRAY® TYPER 4.0 software.
Results: We observed positive staining for TP53 in the 52% of the cases, for p16 in the 81%, for EGFR in the 32% and nuclear β-Catenin was positive in the 20%. FISH demonstrated cytogenetic alterations, like gene amplification or chromosome polysomy in the 32% of samples for EGFR. No deletions or traslocations were observed. No one of the 15 samples sequenced for the Exon 3 of CTNNB1 gene showed any mutation. In total 27 mutations of 9 different oncogenes have been detected in 17 different samples: 2% of samples shown mutations in AKT and BRAF (1 case); 5% in EGFR, MET and NRAS (2 cases); 7% in KIT (3 cases); 10% in KRAS and PDGFRα (4 cases); 20% in PIK3CA (8 cases).
Conclusions: The molecular alterations found in our ECSs suggest that, together with p53, two main pathways could be implicated in the pathogenesis of this neoplasia, like the PIK3CA-AKT and the EGFR-NRAS-KRAS pathways. Supporting by grants from: ISCIII: PI07/90324, PI 080971; RD06/0020/0013; PI-0384/2007; P07-CVI-03100.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 178, Wednesday Afternoon