title: MiR-205 and MiR-375 microRNA assays to distinguish squamous cell carcinoma from adenocarcinoma in lung cancer biopsies.
abstract: BACKGROUND
  Identification of adenocarcinoma (AC) and squamous cell carcinoma (SCC) histology of non-small-cell lung cancer (NSCLC) in biopsies is clinically important but can be inaccurate by routine histopathologic examination. We quantify this inaccuracy at a cancer center, and evaluate the utility of a microRNA-based method to histotype AC/SCC in biopsies.
  
  
  METHODS
  RNA was extracted from tissue sections with greater than 90% tumor content that were macro- or micro-dissected from formalin-fixed, paraffin-embedded biopsy specimens. MicroRNAs in RNA from the biopsies and from resected tumors were quantified by TaqMan reverse transcription-polymerase chain reaction assays and normalized against the RNU6B housekeeping RNA. Publicly available microRNA expression datasets were examined.
  
  
  RESULTS
  NSCLC subtyping of small biopsy specimens by routine histopathologic examination either failed or mistyped the histology of 21% of 190 cases. Using 77 resectates, an reverse transcription-polymerase chain reaction-based assay of microRNAs miR-21, miR-205, and miR-375 was developed to identify AC and SCC subtypes of NSCLC. This method identified the AC/SCC histotypes of 25 biopsies with an accuracy of 96%, and correctly histotyped all 12 cases for which the histology had been mistyped by routine histopathologic examination of the biopsy. Examination of publicly available datasets identified miR-205 and miR-375 as microRNAs with the best ability to histotype AC and SCC, and that levels of the two microRNAs in AC or SCC are unaffected by the pathologic stage of the tumor or the age or race of the patient.
  
  
  CONCLUSIONS
  Histotypic microRNA assays can aid the subtyping of NSCLC biopsies as AC or SCC by standard histopathologic methods.
authors.affiliation: *Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263; †University of Minnesota, Minneapolis, MN 55455; and ‡Lehigh Valley Surgical Oncology, Bethlehem, PA 18017.
authors.forename: Santosh
authors.initials: S
authors.lastname: Patnaik
authors.forename: Reema
authors.initials: R
authors.lastname: Mallick
authors.forename: Eric
authors.initials: E
authors.lastname: Kannisto
authors.forename: Rohit
authors.initials: R
authors.lastname: Sharma
authors.forename: Wiam
authors.initials: W
authors.lastname: Bshara
authors.forename: Sai
authors.initials: S
authors.lastname: Yendamuri
authors.forename: Samjot Singh
authors.initials: SS
authors.lastname: Dhillon
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D001681:Biological Assay; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; C534425:MIR205, human; C540933:MIRN375 microRNA, human