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

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. 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. 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. 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. 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.