Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for differential diagnosis in distinguishing primary adenocarcinomas of the lung from extrathoracic origins. We previously reported the first case of lung metastasis of colorectal origin, with nuclear expression of TTF-1. As most previous studies were performed on series of extrathoracic primary tumors, we raised the question of a possible role of lung microenviroment in TTF-1 expression. We investigated the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas and compared results of immunohistochemistry performed with different primary antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41 (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar nuclear staining in primary and/or other extrathoracic metastatic sites as well as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity between two sets of antibodies was compared in 86 primary pulmonary adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with Novocastra's antibody and 56 cases (65%) with Dako's. Significant discordance was observed (Po 0.01). These results suggest that the diagnostic virtue of TTF-1 detection depends on the used antibody's clone. The SPT24 clone seems to have a stronger affinity for TTF-1 protein but may lead to a few positive colorectal adenocarcinomas. Keywords: TTF-1; lung; carcinoma; metastasis; colorectal Thyroid transcription factor-1 (TTF-1) is a tissuespecific transcription factor expressed in the epithelial cells of thyroid and lung (type II pneumocytes and Clara cells). Carcinomas arising from lung and thyroid also show frequent TTF-1 expression. 1,2 As the lung is one of the most common sites of metastasis, TTF-1 is considered as a reliable marker to distinguish between primary lung carcinoma and lung metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. [3][4][5][6] It is also considered as a reliable marker in the differential diagnosis between pleural localization of lung origin carcinoma and malignant mesothelioma. 7 Two main commercial available clones of monoclonal antibodies have been raised against TTF-1 for immunohistochemical use, 8G7G1/1 and SPT24, their diagnostic value in determining the lung or thyroid origin of adenocarcinoma has not yet been compared. Most of the studies show the high specificity of TTF-1 detection and have been published used the 8G7G1/1 clone. We previously reported one case of lung metastasis of colorectal origin, which showed a focal nuclear staining with the anti-TTF-1 antibody (clone SPT24)...
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