MiR-205 and MiR-375 microRNA assays to distinguish squamous cell carcinoma from adenocarcinoma in lung cancer biopsies

J Thorac Oncol. 2015 Mar;10(3):446-53. doi: 10.1097/JTO.0000000000000423.


Introduction: 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.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Biological Assay
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cohort Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers, Tumor
  • MIRN205 microRNA, human
  • MIRN375 microRNA, human
  • MicroRNAs
  • RNA, Messenger