Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade

Aims: To assess cytokeratin (CK) and thyroid transcription factor (TTF)-1 expression in primary epithelial lung tumours by comparison with non-pulmonary carcinomas and to correlate it with their histological type and grade. Methods and results: Immunohistochemistry using antibodies against CKs 5/6, 7, 19, 20 and TTF-1 was applied to 165 primary and 37 secondary epithelial lung tumours. CK5/6 is a sensitive and specific marker of lung squamous carcinomas being positive in 100% of cases. CK7 is a common marker of primary lung adenocarcinomas (100% of cases) but with a lower specificity since it is also observed in other primary lung carcinomas (70% of large-cell neuroendocrine carcinomas, 40% of large-cell carcinomas, 23% of squamous carcinomas) but also in 27% of non-pulmonary adenocarcinomas. Addition of an anti-CK20 may be useful to prove or disprove the pulmonary origin of an adenocarcinoma when there is a history of colon cancer. CK19 is ubiquitous but a predominant or exclusive 'dot-like' pattern is very suggestive of high-grade neuroendocrine carcinoma. TTF-1 is a very sensitive and specific marker to document the pulmonary origin of an adenocarcinoma if a thyroid origin is excluded. Its expression in neuroendocrine lung tumours depends on the tumour grade. Conclusions: Immunohistochemical expression of CKs and TTF-1 may be correlated with histological type and grade of lung primary epithelial tumours and may allow them to be distinguished from non-pulmonary carcinomas.