Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component
Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component
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DOI：
10.1038/modpathol.2011.88
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发表时间：
2011-10-01
期刊：
影响因子：
7.5
通讯作者：
Hollema, Harry
中科院分区：
文献类型：
--
作者：
de Jong, Renske A.;Nijman, Hans W.;Hollema, Harry
子宫癌性肉瘤（恶性混合苗勒管肿瘤）是一种罕见的侵袭性恶性肿瘤，由上皮（癌）和间质（肉瘤）肿瘤组成，被认为是化生性子宫内膜癌。本研究旨在探讨子宫癌的分子生物学特征和临床表现，为今后治疗方案的改进提供参考。应用免疫组织化学方法检测40例子宫癌组织中雌激素受体α和β、孕激素受体A和B、MLH 1、MSH 2、MSH 6、PTEN（10号染色体缺失的磷酸酶和张力蛋白同源物）、p53、β-连环蛋白和细胞周期蛋白D1的表达。比较上皮和间叶肿瘤成分之间的免疫染色。为了确定上皮成分的预后作用，我们比较了类胶质瘤和非类胶质瘤上皮成分患者的临床病理学数据和生存率。为了确定与高危子宫内膜癌相比，癌性肉瘤的预后，比较这些患者的临床病理特征和生存率。激素受体表达很少发生：雌激素受体-α（8%）和-β（32%），孕激素受体-A（0%）和-B（23%），其次是β-连环蛋白（4%）和细胞周期蛋白D1（7%）。PTEN、MLH 1、MSH 2和MSH 6突变的发生率分别为39%、33%、22%和21%（基于无免疫染色）。p53蛋白的过度表达率为38%。p53、MSH 2和MSH 6的表达模式在上皮性和间叶性肿瘤组分之间相对应。在我们的队列中，上皮成分引起了大多数转移（72%）和血管浸润（70%）。与类上皮成分相比，非类上皮成分患者的生存率往往更差（5年生存率：分别为26%和55%）。与高危子宫内膜癌（3级子宫内膜样癌和非子宫内膜样癌）相比，子宫癌患者的生存率更差; 5年生存率分别为42%、77%和57%。我们的结果支持子宫癌肉瘤的单克隆起源。上皮成分通过引起大部分转移和血管浸润来决定预后。为了改善预后，治疗应侧重于子宫癌肉瘤的上皮性肿瘤成分。Modern Pathology（2011）24，1368-1379; doi：10.1038/modpathol.2011.88; 2011年5月13日在线发表
Carcinosarcomas (malignant mixed Mullerian tumors) of the uterus are rare and aggressive malignancies consisting of an epithelial (carcinoma) and a mesenchymal (sarcoma) tumor component and are considered as metaplastic endometrial carcinomas. This study evaluated molecular characteristics and clinical behavior of uterine carcinosarcomas to improve treatment regimens in the future. Immunohistochemical expression of estrogen receptor-alpha and -beta, progesterone receptor-A and -B, MLH1, MSH2, MSH6, PTEN (phosphatase and tensin homolog deleted on chromosome 10), p53, beta-catenin and cyclin D1 was determined in 40 uterine carcinosarcomas. Immunostaining was compared between epithelial and mesenchymal tumor components. To determine the prognostic role of the epithelial component, clinicopathological data and survival were compared between patients with endometrioid and non-endometrioid epithelial tumor components. To determine prognosis of carcinosarcomas compared with high-risk endometrial carcinomas, clinicopathological characteristics and survival were compared between these patients. Hormone receptor expression occurred infrequently: estrogen receptor-alpha (8%) and -beta (32%), progesterone receptor-A (0%) and -B (23%), next to beta-catenin (4%) and cyclin D1 (7%). PTEN, MLH1, MSH2 and MSH6 mutations occurred in 39%, 33%, 22% and 21%, respectively (based on absent immunostaining). Overexpression of p53 was observed in 38%. Expression patterns of p53, MSH2 and MSH6 corresponded between epithelial and mesenchymal tumor components. In our cohort, the epithelial component caused the majority of metastases (72%) and vascular invasion (70%). Survival tended to be worse for patients with a non-endometrioid epithelial component compared with an endometrioid epithelial component (5-year survival: 26% and 55%, respectively). Survival was worse for patients with uterine carcinosarcomas compared with high-risk endometrial carcinomas (grade 3 endometrioid and non-endometrioid); 5-year survival rates: 42%, 77% and 57%, respectively. Our results support the monoclonal origin of uterine carcinosarcomas. The epithelial component determines prognosis by causing the majority of metastases and vascular invasion. To improve prognosis, treatment should focus on the epithelial tumor component of uterine carcinosarcomas. Modern Pathology (2011) 24, 1368-1379; doi:10.1038/modpathol.2011.88; published online 13 May 2011