title: Ribonucleic Acid In Situ Hybridization Is a More Sensitive Method Than Immunohistochemistry in Detection of Thyroid Transcription Factor 1 and Napsin A Expression in Lung Adenocarcinomas.
abstract: BACKGROUND
  TTF-1 and napsin A immunomarkers have a crucial role in differentiating lung adenocarcinoma from lung squamous cell carcinoma and in identifying a primary lung adenocarcinoma when working on a tumor of unknown origin.
  
  
  OBJECTIVE
  To investigate the diagnostic sensitivity of ribonucleic acid in situ hybridization (RNAscope) in the detection of expression of these biomarkers in lung adenocarcinomas and to compare RNAscope to immunohistochemical techniques.
  
  
  METHODS
  Both RNAscope and the immunohistochemical assays for TTF-1 and napsin A were performed on tissue microarray sections containing 80 lung adenocarcinomas and 80 lung squamous cell carcinomas. The RNAscope assay for both TTF-1 and napsin A was also performed on 220 adenocarcinomas from various organs.
  
  
  RESULTS
  The RNAscope assay for TTF-1 gave positive results in 92.5% (74 of 80) of the lung adenocarcinomas; in contrast, immunohistochemistry gave positive results in 82.5% (66 of 80) of those cases. The RNAscope assay for napsin A gave positive results in 90% (72 of 80) of lung adenocarcinomas; immunohistochemistry results were positive in 77.5% (62 of 80) of those cases. Napsin A expression was not seen in lung squamous cell carcinomas by either method. In contrast, TTF-1 expression was seen in 3.8% (3 of 80) (1(+)) and 10% (8 of 80) (1(+)) of the squamous cell carcinomas by immunochemistry and the RNAscope, respectively. All nonpulmonary adenocarcinoma results were negative for TTF-1 by the RNAscope assay.
  
  
  CONCLUSIONS
  Preliminary data suggest that RNAscope is superior to immunohistochemistry in detecting TTF-1 and napsin A expression in primary lung adenocarcinomas. Therefore, performing an RNAscope assay may be considered for both TTF-1(-) and napsin A(-) cases with a clinical suspicion of lung adenocarcinoma. The TTF-1 results should be interpreted with caution because a small percentage of squamous cell carcinomas can be focally positive by either assay.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Shi
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.forename: Zongming
authors.initials: Z
authors.lastname: Chen
authors.forename: Ming-Xiao
authors.initials: MX
authors.lastname: He
authors.forename: Yuling
authors.initials: Y
authors.lastname: Luo
authors.affiliation: From the Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania (Drs Shi, Liu, Chen, and Lin); and the Department of Research and Development, Advanced Cell Diagnostics, Inc, Hayward, California (Drs Ma, He, and Luo).
authors.forename: Fan
authors.initials: F
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D016282:Aspartic Acid Endopeptidases / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012680:Sensitivity and Specificity; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human