Forkhead box A2 transcription factor is expressed in all types of neuroendocrine lung tumors.

Forkhead box A2 (Foxa2) is a winged helix nuclear transcription protein that regulates the expression of genes that are critical to lung morphogenesis, differentiation, and function, including thyroid transcription factor-1, surfactant proteins, and Clara cell secretory protein. We examined the immunoreactivity of Foxa2 in paraffin sections of 75 lung tumors: 17 typical carcinoids, 2 atypical carcinoids, 4 large cell neuroendocrine (NE) carcinomas, 23 small cell carcinomas, 19 adenocarcinomas, 7 squamous cell carcinomas, and 3 (non-NE) large cell carcinomas, using a polyclonal rabbit Foxa2 antibody and a biotin-streptavidin detection system. In the adjacent lung, Foxa2 was detected in normal and hyperplastic type II cells. Foxa2 immunoreactivity was detected in 13 typical carcinoids (76%), 2 atypical carcinoids (100%), 2 large cell NE carcinomas (50%), 11 small cell carcinomas (48%), and 1 adenocarcinoma (5%). Squamous cell carcinomas and (non-NE) large cell carcinomas uniformly lacked Foxa2 staining. Expression of Foxa2 in the entire spectrum of NE lung tumors is another indication of differentiation shared by typical carcinoid, atypical carcinoid, large cell NE carcinoma, and small cell carcinoma.