RESUMO
Ovarian carcinosarcomas (OCS), also known as malignant mixed mesodermal/Müllerian tumors, are rare neoplasms (1%-4% of all malignant ovarian tumors) composed of high-grade malignant epithelial and mesenchymal elements. OCS occurs in older women. It is associated with a poor outcome and is usually not involved in inherited cancer syndromes. We present 2 cases of OCS; one arising in a patient with a pathogenetic BRCA1 mutation and the other in a woman affected by Lynch Syndrome (LS) carrying a MSH6 germline mutation. To the best of our knowledge, this is the first time that this second type of case has been reported. In this study, we investigated somatic impairment of the wild-type BRCA1 and MSH6 alleles in the OCS of these 2 patients. We also explored in both OCS, the occurrence of TP53 loss of function, which is a genetic alteration known to occur in BRCA-linked ovarian tumorigenesis but not in LS tumors. Moreover, we also provide further data about the histogenesis of OCS.
Assuntos
Proteína BRCA1/genética , Carcinossarcoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/genética , Adulto , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Feminino , Aconselhamento Genético , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Ovário/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
This work has evaluated the potential superiority of a morphomolecular classification based on the combination of clinicopathologic and molecular features of colorectal cancers. A cohort of 126 colorectal carcinomas was investigated by unsupervised hierarchical clustering analysis to combine 13 routinely assessed clinicopathologic features and all five molecular markers recently suggested by Jass' classification to distinguish four molecular subtypes of sporadic colorectal carcinomas. Survival analysis was assessed by a Cox proportional hazards model. A clear separation into three prognostically significant groups was identified: cluster A and cluster C were associated with good prognosis and cluster B with poor prognosis (P=0.006). Clinicopathologic and molecular features of cluster A and cluster B tumors were strongly concordant with colorectal cancer profiles characterized by microsatellite instability or by chromosomal instability, respectively. The clinicopathologic features of cluster C tumors were suggestive of a less aggressive disease than cluster B tumors. Genetically, they appeared intermediate between cluster A and cluster B tumors, as they were mainly microsatellite stable tumors showing high levels of both MGMT methylation and loss of heterozygosity. Chromosomal instability was significantly lower in cluster C than in cluster B tumors. A more accurate tumor classification should combine the prognostic power of clinicopathologic parameters with molecular biomarkers that provide information regarding the natural history of the cancer. Hierarchical clustering seems to be a useful, promising and powerful tool for further translational studies and should lead us to define a diagnostic and prognostic signature for different carcinomas.