Immunohistochemical staining for thyroid transcription factor-1: a helpful aid in discerning primary site of tumor origin in patients with brain metastases.

Metastatic carcinoma of unknown primary origin is a perplexing but common problem, accounting for up to 10% to 15% of all solid tumors at presentation. Many of these metastases presumably arise from primary lung carcinomas, but the morphologic features and immunohistochemical profile of lung cancer is often too nonspecific to permit unequivocal confirmation. Thyroid transcription factor-1 (TTF-1) is expressed in lung adenocarcinomas and thyroid carcinomas but not in adenocarcinomas arising from other sites. For patients with adenocarcinomas in the lung, TTF-1 staining is now routinely used to distinguish a primary lung cancer from a lung metastasis. Along these same lines, TTF-1 staining might prove useful in localizing the tumor origin of adenocarcinomas encountered outside of the lung. The archival surgical pathology files of The Johns Hopkins Hospital were searched for cases of brain metastases biopsied between 1990 and 2000. Tissue blocks were obtained and immunoperoxidase staining was performed using the TTF-1 antibody. The medical records were reviewed independent of the staining results to determine site of tumor origin. Seventy-five patients underwent biopsies of carcinomas metastatic to the brain. At the time of brain biopsy, the primary site of tumor origin was known in 45 cases and unknown in 30 cases. Ultimately, the primary site was established on clinical and radiographic grounds in 71 cases (95%). These included 40 (56%) metastases from a primary lung carcinoma and 31 (44%) metastases from some nonpulmonary carcinoma. TTF-1 staining was present in 31 of the 40 (78%) metastatic lung carcinomas, but in only 1 of the 31 (3%) metastatic nonpulmonary carcinomas (a small-cell carcinoma of the sinonasal tract). When the metastatic lung carcinomas were subtyped, TTF-1 staining was noted in 11 of 11 (100%) adenocarcinomas, in 6 of 7 (86%) small-cell carcinomas, in 15 of 19 (79%) large-cell carcinomas, and in none of 3 (0%) squamous cell carcinomas. TTF-1 staining is very reliable in discerning whether a brain metastasis has arisen from a pulmonary or nonpulmonary site, particularly when dealing with adenocarcinomas and large-cell carcinomas. TTF-1 immunohistochemistry could focus the search for the primary tumor for patients presenting with brain metastasis as the initial manifestation.