PHOX2B

Immunohistochemistry

Essential for the differentiation and survival of sympathetic neurons and chromaffin cells, the transcription factor PHOX2B is highly specific for the peripheral autonomic nervous system. Neuroblasts are derived from sympathoadrenal lineage neural crest cells and therefore require and constitutively express PHOX2B. PHOX2B immunohistochemical staining, as a marker of neural crest derivation, has been shown to be sensitive and specific for undifferentiated neuroblastoma, enabling identification where other markers fail to recognize neuroblastoma among various different small round blue cell tumors of childhood.

The diagnostic utility of PHOX2B staining extends to later stages of differentiation. Its strength and specificity can detect the small foci of neuroblastic tumors metastatic to the bone marrow, an identification critical for determining disease staging. PHOX2B staining also overcomes frequent obstacles to neuroblastoma detection in post-treatment samples, which frequently exhibit dense fibrosis, prominent inflammatory infiltrates, and/or diffuse calcification.

Pathology

Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschsprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia. In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.

Research

Organisations involved in researching Phox2B include those concerned with Congenitial Central Hypoventilation Syndrome. These include Keep Me Breathing based in the UK and The CCHS Network based in the USA. The CCHS Network held a scientific conference in September 2023, which covered significant research into Phox2B and CCHS with Keep Me Breathing presenting, too.

References

References

1. "Entrez Gene: paired-like homeobox 2b".
2. (August 2012). "PHOX2B immunolabeling: a novel tool for the diagnosis of undifferentiated neuroblastomas among childhood small round blue-cell tumors". The American Journal of Surgical Pathology.
3. (April 2015). "Diagnostic utility of PHOX2B in primary and treated neuroblastoma and in neuroblastoma metastatic to the bone marrow". Archives of Pathology & Laboratory Medicine.
4. (November 2017). "PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours". Histopathology.
5. (March 2018). "Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients". Histopathology.
6. Hata et al. (2015).
7. "CCHS for Professionals – Keep Me Breathing".
8. "2023 CCHS Science Conference".