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

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.

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.

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.

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.