Genetic analysis of the early natural history of epithelial ovarian carcinoma.
Genetic analysis of the early natural history of epithelial ovarian carcinoma.
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DOI：
10.1371/journal.pone.0010358
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发表时间：
2010-04-26
期刊：
影响因子：
3.7
通讯作者：
Boyd J
中科院分区：
文献类型：
--
作者：
Pothuri B;Leitao MM;Levine DA;Viale A;Olshen AB;Arroyo C;Bogomolniy F;Olvera N;Lin O;Soslow RA;Robson ME;Offit K;Barakat RR;Boyd J
与上皮性卵巢癌（EOC）相关的高死亡率反映了通常在晚期诊断，但由于这种恶性肿瘤的组织学起源和早期自然病史的不确定性，阻碍了早期检测的改进。在这里，我们报告了对正常人类卵巢组织和早期癌症的分子遗传学和形态学分析，来自BRCA突变携带者和普通人群，表明EOCs通常来自上皮包涵囊肿内的发育不良前体病变。在病理正常的卵巢中，在上皮包涵性囊肿中观察到特异性的致癌应激分子证据。为了进一步探索卵巢肿瘤发生的潜在早期事件，我们对未知卵巢癌高风险女性的卵巢组织进行了激光弹射显微解剖和基因表达谱分析。这些研究表明，与表面上皮相比，良性卵巢囊包涵上皮具有准肿瘤的表达特征，特别是在影响信号转导、细胞周期控制和有丝分裂纺锤体形成的基因方面。与该基因表达谱一致，与表面上皮相比，病理组织学正常的卵巢囊肿细胞增殖指数（细胞增殖增加，细胞凋亡减少）显著提高。此外，在正常卵巢囊上皮中经常发现非整倍体，而在表面上皮中则没有。综上所述，这些数据表明卵巢囊肿性包涵体中经常出现EOC，在此之前存在可识别的发育不良前体病变，细胞增殖增加、细胞凋亡减少和非整倍体可能代表卵巢肿瘤发生的早期畸变。
The high mortality rate associated with epithelial ovarian carcinoma (EOC) reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy. Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasi-neoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis) was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium. Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
DOI：
10.1097/pas.0b013e3181cf3d79
发表时间：
2010-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kurman RJ;Shih IeM
通讯作者：
Shih IeM
影响因子：
6.4
作者：
HUTSON, R;RAMSDALE, J;WELLS, M
通讯作者：
WELLS, M
影响因子：
4.7
作者：
Leitao, MM;Soslow, RA;Boyd, J
通讯作者：
Boyd, J
影响因子：
120.7
作者：
Boyd, J;Sonoda, Y;Hoskins, WJ
通讯作者：
Hoskins, WJ