Histogenesis of carcinosarcoma of the uterine corpus

子宫癌是一种较少见的肿瘤，仅占子宫恶性肿瘤的不到10%。对于子宫癌的发病机制，人们提出了三种学说(碰撞肿瘤学说、联合肿瘤学说和组合肿瘤学说)。我们应用分子生物学技术研究了子宫癌肉瘤的发病机制。分析了X染色体失活的模式，针对恶性上皮性肿瘤和间叶性组织中人类雄激素受体(HUMARA)外显子1的一部分。同时分析了P53和K-ras突变的存在。从癌性肉瘤的上皮性和非上皮性病变中提取DNA。用甲基化敏感限制性内切酶(HHA I或HPA II)处理后，用针对Humara基因位点的嵌套引物进行聚合酶链式反应。我们发现85%的癌肉瘤是联合瘤，15%的癌肉瘤是碰撞瘤。p53基因和K-ras基因的突变分别出现在32%和24%的肿瘤中。我们将单个癌肉瘤的组织发生与临床结果相关联，发现碰撞瘤的预后比联合瘤差。这些观察表明，用分子标记来确定单个癌肉瘤的组织起源可能是有价值的，因为这一结果可以帮助预测单个病例的预后，帮助指导临床治疗。我们进一步应用我们的方法来确定乳腺癌肉瘤的组织起源，以指导临床治疗阴道和卵巢的肿瘤，表明这些肿瘤中的大多数也是联合肿瘤。

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.