Expression of Thyroid Transcription Factor-1, Cytokeratin 7, and Cytokeratin 20 in Bronchioloalveolar Carcinomas: an Immunohistochemical Evaluation of 67 Cases

Distinguishing primary pulmonary adenocarcinoma from metastatic adenocarcinoma involving the lung is a common challenging task. The distinction between mucinous bronchioloalveolar carcinoma (BAC) and metastatic mucinous carcinoma of other sites, in particular, is difficult by routine histology. Immunohistochemical expression of thyroid transcription factor-1 (TTF-1), as well as cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20), has proven diagnostic utility in discerning primary from metastatic neoplasms in the lung. Rigorous studies assessing the expression of these markers in BACs, particularly in regard to nonmucinous and mucinous subtypes, have not been performed. In this study, we evaluated the immunohistochemical expression of TTF-1, CK 7, and CK 20 in 67 BACs (48 nonmucinous, 12 mucinous, and 7 of mixed histology). Overall, 42 (63%) of the 67 BACs were positive for TTF-1. When stratified according to subtype, all 12 mucinous BACs were observed to be TTF-1 negative. This trend toward absence of TTF-1 expression in mucinous areas was also maintained among tumors with mixed histology. Sixty-three (94%) of 67 BACs were CK 7 positive, with no differences in expression observed upon subtype stratification. Three cases were noted to be positive for CK 20; all exhibited mucinous morphology. These results indicate that in contrast to the immunophenotypic profile exhibited by most pulmonary neoplasms, mucinous BACs are TTF-1 negative and may express CK 20. This suggests that in the context of differentiating mucinous BACs from extrapulmonary mucinous tumors metastatic to the lung, evaluation of TTF-1 and CK 20 expression may have limited diagnostic utility.