Simultaneous expression of TTF1 and GATA3 in a lung biopsy sample: confusion in diagnostic pathology.

Background: In daily work, pathologists often use TTF1 and GATA3 in the differential diagnosis of primary lung adenocarcinoma (TTF1+ GATA3-) and metastatic bladder cancer (or breast cancer) (TTF1- GATA3+). However, we encountered a small lung biopsy sample of TTF1+ GATA3+ (clinically suggesting both lung and bladder occupancy), and the dyeing results caused us great confusion; thus, we intended to determine the expressions of TTF1 and GATA3 in lung and bladder cancer by expanding the sample. Methods: The study included a complete case report and the tissue microarrays including pulmonary squamous cell carcinomas (n = 55), lung adenocarcinomas (n = 47), high-grade (n = 68) and low-grade (n = 43) urothelial carcinomas of the bladder. TTF1 and GATA3 immunohistochemical staining were performed on the tissue microarrays, and the relevant literature was retrieved. Results: Our staining results on tissue microarrays showed that TTF1 was expressed in pulmonary adenocarcinomas (44/47, 93.6%), squamous cell carcinomas (1/55, 1.8%), low-grade (1/43, 2.3%) and high-grade (2/68, 2.9%) urothelial carcinomas; GATA3 was only expressed in urothelial carcinomas of the bladder (high-grade: 48/68, 70.6%; low-grade: 42/43, 97.7%). Our literature search results showed that TTF1 could be expressed in a very small number of bladder urothelial carcinomas, and GATA3 could be expressed in a few primary lung squamous cell carcinomas and a very small number of primary lung adenocarcinomas. Conclusions: TTF1 and GATA3 are good markers in the differential diagnosis of primary non-small cell lung cancer (GATA3-) and metastatic urothelial carcinoma of the bladder (GATA3+). However, pathologists should pay attention to a few special cases: lung cancer may express GATA3, and urothelial carcinoma may express TTF1. In these cases, some additional immunohistochemical markers, such as napsin A and URO III, should be added to assist the diagnosis.