Histogenesis of carcinosarcoma of the uterine corpus

子宫腺癌相对少见，占子宫恶性肿瘤的不到10%。关于这些肿瘤的发病机制，目前提出了三种理论（碰撞肿瘤理论、组合肿瘤理论和组合肿瘤理论）。我们应用分子技术确定子宫癌肉瘤的发病机制。我们分析了x染色体失活的模式，目标是恶性上皮和间充质成分中人类雄激素受体（HUMARA）外显子1的一部分。还分析了p53和K-ras突变的存在。从癌肉瘤的上皮和非上皮病变中获得dna。用甲基化敏感限制性内切酶（Hha I或Hpa II）处理后，利用巢式引物对HUMARA位点进行PCR扩增。我们证明85%的癌肉瘤代表合并肿瘤，其中15%代表碰撞肿瘤。p53基因和K-ras基因突变分别在32%和24%的肿瘤中发现。我们将个体癌肉瘤的组织发生与临床结果联系起来，发现碰撞肿瘤的预后比合并肿瘤差。这些观察结果表明，利用分子标志物测定癌肉瘤个体的组织发生可能是有价值的，因为其结果可以帮助预测个体的预后并指导临床管理。我们进一步应用我们的方法来确定乳腺、阴道和卵巢癌肉瘤的组织发生，发现这些肿瘤中的大多数也代表了合并肿瘤。

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.