Shedden Kerby A, Kshirsagar Malti P, Schwartz Donald R, Wu Rong, Yu Hongfeng, Misek David E, Hanash Samir, Katabuchi Hidetaka, Ellenson Lora Hedrick, Fearon Eric R, Cho Kathleen R
Department of Statistics, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
Clin Cancer Res. 2005 Mar 15;11(6):2123-31. doi: 10.1158/1078-0432.CCR-04-2061.
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 beta-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.
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.
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 beta-catenin defects show a common gene expression signature largely distinct from that seen in tumors lacking such defects.
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.
卵巢癌和子宫癌呈现出几种分化模式，类似于在生殖道非肿瘤性上皮中所见的模式。特定的癌基因和肿瘤抑制基因缺陷与子宫或卵巢发生的癌的特定分化模式相关。例如，具有子宫内膜样分化的卵巢癌和子宫癌经常显示β-连环蛋白突变。虽然分化类型在子宫癌治疗中被考虑，但目前它对卵巢癌治疗决策没有贡献。一种广泛接受的观点是，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。
使用寡核苷酸微阵列评估103例原发性卵巢癌和子宫癌中的基因表达，我们试图探讨起源器官或分化类型（组织学类型；子宫内膜样与浆液性）对基因表达模式是否有更显著的影响。
我们发现，起源器官和组织学类型对基因表达的影响在程度上相似，并且是平行的，即两种组织学类型中的器官影响相似，两种器官中的组织学类型影响相似。此外，具有β-连环蛋白缺陷的卵巢和子宫子宫内膜样腺癌显示出一种共同的基因表达特征，与缺乏此类缺陷的肿瘤中所见的特征有很大不同。
我们的结果说明了起源器官、分化类型和特定分子缺陷如何都对最常见类型的卵巢癌和子宫癌中的基因表达产生影响。这些发现还意味着基因表达数据对于将卵巢癌患者分层以采用新的治疗方法将具有价值。
