[Thyroid transcription factor-1 in pulmonary cytology]

Currently it is necessary to define in almost each case whether a carcinoma is a small or non-small cell carcinoma, adenocarcinoma, pulmonary or metastatic in origin. Thyroid transcription factor-1 (TTF-1) was positive in more than 80% of primary pulmonary adenocarcinomas and in none from the sites other than the thyroid. Mucinous bronchioloalveolar carcinomas are usually negative. Immunocytochemistry with a panel of cytokeratins (CK) 7 and 20, along with TTF-1, is recommended for identification of the origin of adenocarcinoma in pulmonary cytology.

The aim of the study was to assess the value of TTF-1 reactivity in adenocarcinomas determined by immunocytochemistry in different pulmonary cytologic specimens.

Cytologic specimens of 83 patients with adenocarcinomas were analyzed. Immunocytochemistry was performed with a panel of antibodies: TTF-1, CK7, CK20 in all cases and CK5/6 if necessary. The study included 17 different bronchoscopic samples (aspirates, brushes, transbronchial FNA), 14 transthoracic FNA, 27 pleural effusions and 25 FNA of peripheral lymph nodes. TTF-1 was positive in 26/83 (31.3%) and negative in 47/83 (68.7%) samples. All TTF-1 positive adenocarcinomas were also CK7 positive, thus being conclusive of pulmonary origin. In TTF-1 negative group, pulmonary origin was proven in 10/57 (17.5%) adenocarcinomas, whereas 18/57 (31.6%) adenocarcinomas were metastatic; in 29/57 (50.9%) adenocarcinomas other diagnostic procedures failed to prove their origin. CK20 positivity with CK7 negativity was conclusive of metastatic gastrointestinal adenocarcinoma.

Numerous reports support TTF-1 expression in adenocarcinoma as being highly specific for pulmonary origin, if thyroid is excluded. We were able to identify 36/83 (43.4%) adenocarcinomas as pulmonary adenocarcinomas. Among them, only 31.3% were TTF-1 positive. In our study, about 60% of adenocarcinomas with uncertain origin were in the groups of pleural effusions and lymph nodes. In these groups, cytologic diagnosis of adenocarcinoma often provided evidence of the carcinoma expansion, aggressive behavior and poor differentiation, and served as a guideline for patient management. In the studies of mixed pulmonary adenocarcinomas, TTF-1 expression was lower in poorly differentiated segments as well as in the areas with bronchioloalveolar pattern. One explanation for the high percentage of TTF-1 negative adenocarcinomas in our material is morphological selection of adenocarcinomas of presumably non-pulmonary origin before immunocytochemistry.

TTF-1 in a panel with cytokeratins is specific for differentiation of the origin of adenocarcinomas. TTF-1 negative finding in adenocarcinomas does not exclude pulmonary origin, but only points to other diagnostic procedures for definitive diagnosis.