Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas.
Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas.
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组织学类型、起源器官和 Wnt 通路状态：对卵巢癌和子宫癌基因表达的影响。
DOI：
10.1158/1078-0432.ccr-04-2061
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Cho,KathleenR
中科院分区：
文献类型：
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作者：
Shedden,KerbyA;Kshirsagar,MaltiP;Schwartz,DonaldR;Wu,Rong;Yu,Hongfeng;Misek,DavidE;Hanash,Samir;Katabuchi,Hidetaka;Ellenson,LoraHedrick;Fearon,EricR;Cho,KathleenR
目的：卵巢癌和子宫癌表现出几种类似于妇科非肿瘤上皮的分化模式。特定的癌基因和抑癌基因缺陷与子宫或卵巢癌的特定分化模式有关。例如，卵巢癌和子宫癌伴类胶质细胞分化经常显示β-连环蛋白突变。尽管在子宫癌的治疗中考虑了分化类型，但目前它并不有助于决定卵巢癌的治疗。一个被广泛接受的观点是，特定基因缺陷和基因表达变化的积累是癌症表型特征的基础，包括它们对治疗的反应。实验设计：使用寡核苷酸微阵列评估103例原发性卵巢癌和子宫癌的基因表达，我们试图解决是否起源器官或分化类型（组织型;类浆液性与浆液性）对基因表达模式有更实质性的影响。我们发现，由于器官的起源和组织型对基因表达的影响是相似的幅度和平行的器官的影响是相似的两个组织型和组织型的影响是相似的两个器官。此外，卵巢和子宫腺瘤样腺癌与β-catenin缺陷表现出一个共同的基因表达的签名，很大程度上不同于在肿瘤中看到的缺乏这样的deficiency.Conclusions：我们的研究结果说明了器官的起源，分化类型，和特定的分子缺陷都有助于基因表达在最常见的类型的卵巢和子宫癌。研究结果还表明，基因表达数据将对卵巢癌患者进行分层，以寻找新的治疗方法具有价值。
Purpose:Ovarian and uterine carcinomas manifest several differentiation patterns resembling those seen in nonneoplastic epithelia of the gynecologic tract. Specific oncogene and tumor suppressor gene defects have been associated with particular differentiation patterns in carcinomas arising in either the uterus or ovary. For instance, ovarian and uterine carcinomas with endometrioid differentiation frequently show β-catenin mutations. Whereas type of differentiation is considered in the treatment of uterine carcinomas, it does not presently contribute to decisions about treatment of ovarian carcinomas. A widely accepted view is that the accumulation of specific gene defects and gene expression changes underlies phenotypic traits of cancers, including their response to treatment.Experimental Design:Using oligonucleotide microarrays to assess gene expression in 103 primary ovarian and uterine carcinomas, we sought to address whether organ of origin or type of differentiation (histotype; endometrioid versus serous) had a more substantial effect on gene expression patterns.Results:We found that effects on gene expression due to organ of origin and histotype are similar in magnitude and are parallel in that organ effects are similar in the two histotypes and histotype effects are similar in the two organs. In addition, ovarian and uterine endometrioid adenocarcinomas with β-catenin defects show a common gene expression signature largely distinct from that seen in tumors lacking such defects.Conclusions:Our results illustrate how organ of origin, type of differentiation, and specific molecular defects all contribute to gene expression in the most common types of ovarian and uterine cancers. The findings also imply gene expression data will be of value for stratifying ovarian cancer patients for new treatment approaches.