Histogenesis of carcinosarcoma of the uterine corpus

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Carcinosacomas of the uterus is relatively uncommon, accounting for less Than 10% of uterine malignancies.Three theories (collision tumor theory, combination tumor theory and composition tumor theory) have been proposed for the pathogenesis of these tumors.We applied molecular techniques to determine the pathogenesis of uterine carcinosarcomas.The patterns of X-chromosome inactivation were analyzed, targeting a portion of exon 1 of the human androgen receptor (HUMARA) in malignant epithelial and mesenchymal components.The presence of p53 and K-ras mutations was also analyzed.DNAs were obtained from both epithelial and non-epithelial lesions from carcinosarcomas.Following treatment with methylation sensitive restriction endonuclease (Hha I or Hpa II), PCR amplification was performed using nested primers targeted to The HUMARA locus.We demonstrated that 85% of carcinosarcomas represent combination tumors, and 15% of those represent collision tumors.Mutations in the p53 gene and K-ras gene were found in 32% and 24% of the tumors, respectively.We correlated the histogenesis of individual carcinosarcomas with clinical outcome, and found that collision tumors had poorer prognosis than combination tumors.These observations show that the determination of histogenesis in individual cases of carcinosarcoma using molecular markers may be worthwhile, since the result could help predict the prognosis of individual cases and help guide clinical management.We further applied our methodology to determine the histogenesis of carcinosarcoma of the breast, vagina and ovary and showed that most of these tumors also represented combination tumors.