Thyroid transcription factor-1 (TTF-1) is a member of the NKX2 family of homeodomain transcription factors. It is expressed in epithelial cells of the thyroid gland and lung. TTF-1 has been shown to be a sensitive (65-81%) and specific marker (94%) in the majority of primary lung adenocarcinomas. Studies have shown that TTF-1, used in combination with Napsin A, provided 93% sensitivity and 100% specificity for lung adenocarcinoma, if CK5 and Desmoglein 3 were both negative in the same case.
CK5 is a type II intermediate filament protein that is expressed in active basal layers of most stratified squamous epithelia. In a published study, rabbit monoclonal CK5 antibody was compared to mouse monoclonal CK5/6. CK5 was 84% sensitive and 100% specific for lung squamous cell carcinoma (SqCC) when compared to CK5/6 (80% sensitivity and 97% specificity). CK6 mRNA has been detected in lung adenocarcinomas; thus CK5 alone, may be a more specific marker than CK5/6. Studies have shown that CK5, used in combination with Desmoglein 3, provided 93.7% sensitivity with 100% specificity for lung SqCC.
TTF-1 (lung adenocarcinoma) is stained with DAB chromogen, and CK5 rabbit monoclonal (lung SqCC) is stained with a Fast Red chromogen. In most lung cancers tested, only a single antibody stain will be observed. Co-expressions of both antibodies may be an indication of adenosquamous cell carcinomas. When used in combination with Desmoglein 3 and Napsin A, a 93% staining sensitivity and 100% specificity was achieved for lung adenocarcinoma, and a 93.7% sensitivity and 100% specificity was achieved for lung SqCC; therefore, the antibody combination of TTF-1 + CK5 is a first class screener for discriminating between lung adenocarcinoma (TTF-1) vs. lung SqCC (CK5).