Diagnostic and prognostic value of TTF-1 (Thyroid Transcription Factor-1) immunohistochemistry in canine malignant lung tumors.

Introduction. Distinguishing primary lung carcinoma (PLC) from metastatic carcinoma involving the lung is a common challenging task. Thyroid transcription factor-1 (TTF-1), a nuclear protein originally identified in follicular cells of the thyroid gland and subsequently in pneumocytes, is a new immunohistochemical marker used in human medicine to recognize carcinoma of pulmonary origin. Methods. 34 canine PLC and 15 non-PLC (13 tumors metastatic to lungs and 2 pleuric mesotheliomas) were investigated immunohistochemically for the expression of TTF-1, to evaluate its diagnostic and prognostic relevance. Results. Strong TTF-1 positivity was observed in the nucleus of pneumocytes of the normal lung adjacent to tumor tissue (internal positive control) in 35 out of the 49 tested cases (20 PLCs and all non-PLCs). 14 PLCs stained negatively, due to overfixation or prolonged storage of paraffin blocks, and were therefore excluded from the study. Among the 20 immunoreactive PLCs (10 papillary adenocarcinomas, 5 bronchiolo-alveolar carcinomas, 2 squamous cell carcinomas, 2 adenosquamous carcinomas and 1 acinar adenocarcinoma), 17 showed strong nuclear positivity, except both squamous cell carcinomas and one papillary adenocarcinoma. In non-PLCs tumor cells were always TTF-1 negative. TTF-1 was 100% specific and 85% sensitive for PLCs. There was no significant relationship among the percentage of labeled tumor cells (TTF-1 index) and the considered clinico-pathologic parameters (age, gender, histopathologic subtype, tumor grade, TNM stage, node status and MIB-1 index). Conclusions. TTF-1 immunohistochemistry may give useful additional information regarding the origin of canine lung tumors, whereas its prognostic utility still remains to be determined.