Back to Search
Start Over
Examination of PHOX2B in adult neuroendocrine neoplasms reveals relatively frequent expression in phaeochromocytomas and paragangliomas.
- Source :
-
Histopathology [Histopathology] 2017 Oct; Vol. 71 (4), pp. 503-510. Date of Electronic Publication: 2017 Jul 13. - Publication Year :
- 2017
-
Abstract
- Aims: Paired-like homeobox 2b (PHOX2B) 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, PHOX2B 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 PHOX2B expression in a large cohort of phaeochromocytomas and paragangliomas, as well as well-differentiated neuroendocrine tumours (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs).<br />Methods and Results: Tissue microarrays (TMAs) were constructed from 609 tumours: 111 phaeochromocytomas, 146 paragangliomas, 250 WDNETs, and 102 PDNECs. PHOX2B immunohistochemistry was scored for extent (%) and intensity (0-3+), and an H-score (extent × intensity) was calculated. PHOX2B 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 WDNETs and only 7% of PDNECs stained, the latter often strongly. In a representative cohort of corresponding whole sections (n = 55), the results in WDNETs and PDNECs were unchanged, whereas half of the phaeochromocytomas/paragangliomas that were negative on TMAs became focally, weakly positive.<br />Conclusions: We found frequent, weak to moderate PHOX2B expression in phaeochromocytomas/paragangliomas and no expression in WDNETs, which could be diagnostically useful in the distinction of these tumours. Expression in a minority of PDNECs probably reflects the transcription factor lineage infidelity that is characteristic of this tumour class.<br /> (© 2017 John Wiley & Sons Ltd.)
- Subjects :
- Adrenal Gland Neoplasms pathology
Adult
Cohort Studies
Homeodomain Proteins genetics
Humans
Neuroblastoma metabolism
Neuroendocrine Tumors pathology
Paraganglioma pathology
Pheochromocytoma pathology
Tissue Array Analysis
Transcription Factors genetics
Adrenal Gland Neoplasms metabolism
Homeodomain Proteins metabolism
Neuroblastoma pathology
Neuroendocrine Tumors metabolism
Paraganglioma metabolism
Pheochromocytoma metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2559
- Volume :
- 71
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Histopathology
- Publication Type :
- Academic Journal
- Accession number :
- 28464318
- Full Text :
- https://doi.org/10.1111/his.13243