title: Expression of mir-21 and mir-143 in cervical specimens ranging from histologically normal through to invasive cervical cancer.
abstract: BACKGROUND
  MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples.
  
  
  RESULTS
  We measured the expression of mir-21 and mir-143 in 142 formalin-fixed, paraffin embedded (FFPE) cervical biopsy tissue blocks, collected from Dantec Oncology Clinic, Dakar, Senegal. MicroRNA expression analysis was performed using Taqman-based real-time PCR assays. Protein immunohistochemical staining was also performed to investigate target protein expression on 72 samples. We found that mir-21 expression increased with worsening clinical diagnosis but that mir-143 was not correlated with histology. These observations were in stark contrast to previous reports involving cervical cancer cell lines in which mir-143 was consistently down-regulated but mir-21 largely unaffected. We also identified, for the first time, that cytoplasmic expression of Programmed Cell Death Protein 4 PDCD4; a known target of mir-21) was significantly lower in women with invasive cervical carcinoma (ICC) in comparison to those with cervical intraepithelial neoplasia (2-3) or carcinoma in situ (CIN2-3/CIS), although there was no significant correlation between mir-21 and PDCD4 expression, despite previous studies identifying PDCD4 transcript as a known mir-21 target.
  
  
  CONCLUSIONS
  Whilst microRNA biomarkers have a number of promising features, more studies on expression levels in histologically defined clinical specimens are required to investigate clinical relevance of discovery-based studies. Mir-21 may be of some utility in predictive screening, given that we observed a significant correlation between mir-21 expression level and worsening histological diagnosis of cervical cancer.
authors.affiliation: HPV Research Laboratory, UW Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Georgios
authors.initials: G
authors.lastname: Deftereos
authors.forename: Simon R
authors.initials: SR
authors.lastname: Corrie
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Feng
authors.forename: Janice
authors.initials: J
authors.lastname: Morihara
authors.forename: Joshua
authors.initials: J
authors.lastname: Stern
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Kiviat
mesh_terms: D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005557:Formaldehyde; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016612:Paraffin Embedding; D016707:Tissue Fixation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C542359:MIRN143 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D005557:Formaldehyde