Comparative immunohistochemical analysis of pulmonary and thymic neuroendocrine carcinomas using PAX8 and TTF-1

Abstract

PAX8 is expressed in thymic epithelial neoplasms and a subset of neuroendocrine carcinomas of gastrointestinal origin but not pulmonary neuroendocrine carcinomas. Thyroid transcription factor 1 (TTF-1) is known to be positive in pulmonary neuroendocrine carcinomas, but studies investigating its expression in thymic neuroendocrine carcinomas are lacking. To date, there are no comprehensive studies focusing on the comparative expression of PAX8 or TTF-1 in pulmonary and thymic neuroendocrine carcinoma. Twenty-five cases of low and intermediate grade neuroendocrine carcinomas of pulmonary and thymic origin, respectively, were selected for immunohistochemical studies using antibodies directed against PAX8 and TTF-1. The percentage of positive tumor cells as well as the intensity of staining were evaluated and scored. Twenty-one of the pulmonary neuroendocrine carcinomas were classified as low grade (typical carcinoid) and 4 as intermediate grade (atypical carcinoid) tumors; the thymic tumors consisted of 8 low grade and 17 intermediate grade neuroendocrine carcinomas. Only 2 (8%) of the pulmonary tumors showed nuclear expression of PAX8 while 19 (76%) expressed TTF-1. Of the thymic tumors, 8 (32%) were positive for PAX8 and 2 (8%) showed TTF-1 positivity. Primary neuroendocrine carcinomas of the thymus are rare neoplasms that display a more aggressive clinical course than pulmonary neuroendocrine carcinomas, highlighting the importance of the separation of these tumors. To date, there are no specific immunomarkers to distinguish between neuroendocrine carcinomas of pulmonary and thymic origin. The differential expression of PAX8 and TTF-1 may prove useful in this context as a PAX8+/TTF-1− immunophenotype appears to be more common in thymic neuroendocrine carcinomas, whereas the reverse (PAX8−/TTF-1+) is true for most pulmonary neuroendocrine carcinomas.