title: MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features.
abstract: BACKGROUND
  MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas.
  
  
  METHODS
  We measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis.
  
  
  RESULTS
  Expression of four miRNAs (miR-30c, miR-30d, miR-30e-3p, miR-370) was significantly different between carcinomas and benign ovarian tissues as well as between carcinoma and borderline tissues. An additional three miRNAs (miR-181d, miR-30a-3p, miR-532-5p) were significantly different between borderline and carcinoma tissues. Expression of miR-532-5p was significantly lower in borderline than in benign tissues. Among ovarian carcinomas, expression of four miRNAs (miR-30a-3p, miR-30c, miR-30d, miR-30e-3p) was lowest in mucinous and highest in clear cell samples. Expression of miR-30a-3p was higher in well-differentiated compared to poorly differentiated tumors (P = 0.02), and expression of miR-370 was higher in stage I/II compared to stage III/IV samples (P = 0.03). In multivariate analyses, higher expression of miR-181d, miR-30c, miR-30d, and miR-30e-3p was associated with significantly better disease-free or overall survival. Finally, lower expression of miR-30c, miR-30d, miR-30e-3p and miR-532-5p was significantly associated with overexpression of Her-2/neu.
  
  
  CONCLUSIONS
  Aberrant expression of miRNAs is common in ovarian tumor suggesting involvement of miRNA in ovarian tumorigenesis. They are associated with histology, clinical stage, survival and oncogene expression in ovarian carcinoma.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea.
authors.forename: Heejeong
authors.initials: H
authors.lastname: Lee
authors.forename: Chul Soo
authors.initials: CS
authors.lastname: Park
authors.forename: Georgios
authors.initials: G
authors.lastname: Deftereos
authors.forename: Janice
authors.initials: J
authors.lastname: Morihara
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Stern
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Swisher
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Feng
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human