Thyroid Transcription Factor-1 Is Not Expressed in Squamous Cell Carcinomas of the Lung: An Immunohistochemical Study With Review of the Literature

Thyroid transcription factor-1 (TTF-1) is one of the peripheral airway epithelial markers that, because it is commonly expressed in lung adenocarcinomas, but not in squamous cell carcinomas, is regarded as being useful in distinguishing between these 2 malignancies, especially in those instances in which the diagnosis cannot be made on routine histology. Even though it is generally believed that TTF-1 is not expressed in squamous cell carcinomas of the lung, a significant number of studies have reported positivity for this marker in up to 38% of the cases investigated. To determine the causes of these discrepancies, 85 pulmonary and 50 nonpulmonary squamous cell carcinomas (17 skin, 8 esophagus, 5 uterine cervix, and 20 from the head-and-neck region) were investigated by immunohistochemistry for TTF-1. None of the 85 squamous cell carcinomas of the lung showed reactivity in the neoplastic cells; however, because strong TTF-1 positivity was observed in the hyperplastic type II pneumocytes that were sometimes seen entrapped within the tumor, it is concluded that the presence of these entrapped cells was one of the most likely causes of the discrepancies. In addition, after a careful review of all of the previous publications on TTF-1 expression in squamous cell carcinomas of the lung, it was found that other factors, such as the type of antibody used and the selection of the cases, may have been the cause of the discrepancies.