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Examination of PHOX 2B in adult neuroendocrine neoplasms reveals relatively frequent expression in phaeochromocytomas and paragangliomas
Author(s) -
Lee John P,
Hung Yin P,
O'Dorisio Thomas M,
Howe James R,
Hornick Jason L,
Bellizzi Andrew M
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13243
Subject(s) - immunohistochemistry , paraganglioma , neuroblastoma , medicine , chromogranin a , pathology , tissue microarray , biology , genetics , cell culture
Aims Paired‐like homeobox 2b ( PHOX 2B) is a transcription factor with expression outside of the central nervous system restricted to neurons and chromaffin cells of the autonomic nervous system. Germline mutations cause congenital central hypoventilation syndrome and predispose to neuroblastoma and Hirschsprung disease. Among paediatric small round cell tumours, PHOX 2B is neuroblastoma‐specific. Two studies of adult autonomic nervous system tumours ( n = 62) produced conflicting results (all tumours stained in one; expression restricted to 40% of paragangliomas in the other). We examined PHOX 2B expression in a large cohort of phaeochromocytomas and paragangliomas, as well as well‐differentiated neuroendocrine tumours ( WDNET s) and poorly differentiated neuroendocrine carcinomas ( PDNEC s). Methods and results Tissue microarrays ( TMA s) were constructed from 609 tumours: 111 phaeochromocytomas, 146 paragangliomas, 250 WDNET s, and 102 PDNEC s. PHOX 2B immunohistochemistry was scored for extent (%) and intensity (0–3+), and an H‐score (extent × intensity) was calculated. PHOX 2B expression was seen in 32% of phaeochromocytomas and in 47% of paragangliomas. Mean/median H‐scores for these tumours were in the 30–55 range (i.e. weak to moderate staining). No WDNET s and only 7% of PDNEC s stained, the latter often strongly. In a representative cohort of corresponding whole sections ( n = 55), the results in WDNET s and PDNEC s were unchanged, whereas half of the phaeochromocytomas/paragangliomas that were negative on TMA s became focally, weakly positive. Conclusions We found frequent, weak to moderate PHOX 2B expression in phaeochromocytomas/paragangliomas and no expression in WDNET s, which could be diagnostically useful in the distinction of these tumours. Expression in a minority of PDNEC s probably reflects the transcription factor lineage infidelity that is characteristic of this tumour class.