MOLECULAR EVIDENCE THAT MOST BUT NOT ALL CARCINOSARCOMAS OF THE UTERUS ARE COMBINATION TUMORS

The pathogenesis of carcinosarcoma is still a subject of controversy, In the present study, molecular techniques were applied to determine t he pathogenesis of uterine carcinosarcomas, The patterns of chromosome X inactivation were analyzed, targeting a portion of exon 1 of the hu man androgen receptor (HUMARA) in malignant epithelial and mesenchymal components, The presence of p53 and K-ras mutations were al(io analyz ed, H&E-stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both epithelial and nonepithelial lesion s from 25 carcinosarcomas, and DNAs were extracted by proteinase 1( di gestion, Following treatment with methylation-sensitive restriction en donuclease (HhaI or HpaII), PCR amplification was performed using nest ed primers targeted to the HUMARA locus, Mutations in the p53 gene and K-ras gene were found in eight (32%) and six (24%) tumors, respective ly, The patterns of chromosome X inactivation were different between t he carcinomatous and sarcomatous components of three carcinosarcomas, indicating that these three tumors represent collision tumors, By cont rast, he patterns of chromosome X inactivation, K-ras sequence, and p5 3 sequence were identical in both carcinomatous and sarcomatous compon ents in 21 carcinosarcomas, indicating that these 21 tumors represent combination tumors, One case produced equivocal results that precluded determination of whether it represented a collision or combination tu mor, These observations show that although most carcinosarcomas are co mbination tumors, some develop as collision tumors, The determination of histogenesis in individual cases of carcinosarcoma using molecular markers may be worthwhile, because the result could help predict the p rognosis of individual cases and help guide clinical management.