77PMolecular: Genetic analysis of uterine carcinosarcomas

Abstract Background Tissue precursors of uterine carcinosarcomas remain unknown, therefore targeted therapy has not been determined. Methods This research is based on the investigation of formalin‐fixed, paraffin‐embedded tissue blocks from 17 women undergoing primary surgical treatment between 1961–2010, that were retrieved from the pathoanatomical department of the Institute of Oncology named after N.N.Petrov. In the present study, molecular investigations were applied to determine the pathogenesis of uterine carcinosarcomas. We have analyzed microsatellite instability, mutations of TP53 (exons 5-9), PTEN (exons 5, 8), K-RAS (exon 1) and loss of heterozygosity of variable loci of the chromosome 17 in epithelial and mesenchymal components of uterine carcinosarcomas. DNAs were extracted by proteinase K digestion («Fisher» US) by Herrington, C.S. & McGee, J.O. Mutations of TP53, PTEN and K-RAS were defined by SSCP with the next sequence. Highly sensitive markers BAT 26 and BAT 40 were used for analysis of microsatellite instability. Results The loss of heterozygosity of variable markers of the short arm of the 17th chromosome was detected (in 9 of 17 tumours- 52,9%). All 17 tumours were microsatellite stable. K-ras mutations were detected in 2 of 17 tumours - 11,7%. One tumour contained identical mutations in both components, other one contained mutations only in the epithelial component. Mutations in the TP53 were identified in 13 of 17 tumours - 76,5%. Five (29,4%) tumours contained identical mutations in both components, 8 (47,1%) - only in the epithelial component and 4 showed wild-type TP53. PTEN mutations were detected in 11 of 17 tumours - 64,7%. Six tumours (35,3%) contained wild-type PTEN. Tumours with PTEN mutations showed worse prospects than ones with wild-type PTEN: 1-yr overall survival - 12,5% vs 60 %, р Conclusions Uterine carcinosarcomas are the microsatellite stable tumours. This type of tumours is associated with chromosomal instability of the genome. PTEN mutations are matched with poor prognosis and low overall survival. The present study of PTEN damages may be important for targeted therapy by the PARP inhibitors. Legal entity responsible for the study Russian Medical Academy for Continuous Professional Education. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.