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 þ /TTF-1 À immunophenotype appears to be more common in thymic neuroendocrine carcinomas, whereas the reverse (PAX8 À /TTF-1 þ ) is true for most pulmonary neuroendocrine carcinomas.

Thymic neuroendocrine tumors (paraganglioma and carcinoid tumors): a comparative immunohistochemical study of 46 cases

“…F, Napsin A is uniformly absent in paragangliomas (×20). our group was able to demonstrate TTF-1 expression in a small subset (8%) of thymic carcinoid tumors [19]. These observations are recapitulated in our current study: all our paragangliomas were negative for TTF-1, whereas 17% of the thymic carcinoid tumors showed diffuse but weak TTF-1 reactivity.…”

“…Immunohistochemically, the tumors are characterized by consistent expression of pancytokeratin, CAM5.2, synaptophysin, chromogranin A, neuron-specific enolase, CD56, and CD57 [1,[14][15][16][17][18]. More recently, Pax8 was found to label not only thymomas and thymic carcinomas but also approximately one third of thymic carcinoid tumors, whereas TTF-1 is only rarely expressed [19]. The survival rate for patients with thymic carcinoid tumors is significantly worse than for patients with pulmonary primaries.…”

A Comprehensive Analysis of Markers for Neuroendocrine Tumors of the Lungs Demonstrates Estrogen Receptor Beta to be a Prognostic Markers in SCLC Male Patients

“…Neuroendocrine markers were detected at high frequency in all tumour subtypes: Synaptophysin in 96%, CgA in 75% (both with cytoplasmatic staining) and TTF1 in 63% of all tumour samples (with nuclear staining), the latter in line with previously reported data [16,17]. At least two markers were expressed in each sample.…”

The Diagnostic Utility of PAX8 for Neuroendocrine Tumors

“…24 However, the thymic development is dependent on the 2 members of the PAX subgroup I: PAX1 and PAX9, rather than PAX8. 8,25 Thus, it was possible that PAX8 immunoreactivity in thymic NETs was caused by the cross-reaction of the PAX8-P antibody to PAX1 or PAX9.…”