title: Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 beta-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.
authors.affiliation: Department of Statistics, Medical School, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Kerby A
authors.initials: KA
authors.lastname: Shedden
authors.forename: Malti P
authors.initials: MP
authors.lastname: Kshirsagar
authors.forename: Donald R
authors.initials: DR
authors.lastname: Schwartz
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Yu
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Katabuchi
authors.forename: Lora Hedrick
authors.initials: LH
authors.lastname: Ellenson
authors.forename: Eric R
authors.initials: ER
authors.lastname: Fearon
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Cho
mesh_terms: D002454:Cell Differentiation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D015534:Trans-Activators; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin