Taylor Nicholas P, Zighelboim Israel, Huettner Phyllis C, Powell Matthew A, Gibb Randall K, Rader Janet S, Mutch David G, Edmonston Tina B, Goodfellow Paul J
Division of Gynecologic Oncology, Washington University School of Medicine and Siteman Cancer Center, St Louis, MO 63110, USA.
Mod Pathol. 2006 Oct;19(10):1333-8. doi: 10.1038/modpathol.3800654. Epub 2006 Jun 30.
Growing molecular evidence shows that uterine carcinosarcomas are clonal tumors. The carcinoma component has a dominant effect in the aggressive clinical behavior of these tumors. Defective DNA mismatch repair affects up to 30% of endometrial adenocarcinomas. The frequency and importance of defective DNA mismatch repair in the histiogenesis of uterine carcinosarcomas remains controversial. We studied the pattern and frequency of defective DNA mismatch repair and TP53 alterations in the epithelial and mesenchymal components of 28 uterine carcinosarcomas. We found evidence of defective DNA mismatch repair in six cases (21%) with a concordance rate of 83% for carcinoma-sarcoma pairs (kappa=0.887, P<0.001). Lack of immunostaining for the MLH1 protein was demonstrated in both components in two of these tumors. TP53 defects were evaluated by 17p deletion analysis and p53 immunostaining. Nineteen carcinoma (68%) and 18 sarcoma (64%) components had evidence of either TP53 allelic loss or p53 overexpression. These defects proved clonal in 76% of cases (kappa=0.602, P=0.003). Our results indicate that defective DNA mismatch repair and TP53 defects are common early events in carcinosarcoma tumorigenesis. The high rate of concordance for these molecular defects between the carcinoma and sarcoma components adds to existing molecular evidence that carcinosarcomas are clonal malignancies.
越来越多的分子证据表明，子宫癌肉瘤是克隆性肿瘤。癌成分在这些肿瘤的侵袭性临床行为中起主导作用。DNA错配修复缺陷影响高达30%的子宫内膜腺癌。DNA错配修复缺陷在子宫癌肉瘤组织发生中的频率和重要性仍存在争议。我们研究了28例子宫癌肉瘤上皮和间叶成分中DNA错配修复缺陷和TP53改变的模式及频率。我们在6例（21%）病例中发现了DNA错配修复缺陷的证据，癌-肉瘤配对的一致性率为83%（kappa=0.887，P<0.001）。在其中2例肿瘤的两个成分中均显示MLH1蛋白免疫染色缺失。通过17p缺失分析和p53免疫染色评估TP53缺陷。19个癌成分（68%）和18个肉瘤成分（64%）有TP53等位基因缺失或p53过表达的证据。在76%的病例中这些缺陷被证明是克隆性的（kappa=0.602，P=0.003）。我们的结果表明，DNA错配修复缺陷和TP53缺陷是癌肉瘤肿瘤发生过程中常见的早期事件。癌和肉瘤成分之间这些分子缺陷的高一致性率进一步证明了癌肉瘤是克隆性恶性肿瘤这一现有分子证据。
