Endocrine Abstracts

Germline mutations account for hereditary phaeochromocytoma (PCC) and paraganglioma (PGL) syndromes. SDHB immunostaining can be used to functionally characterise SDH status on PCC and PGL tumours. Genetic testing of multiple candidate genes is increasingly performed in patients presenting with PCC/PGL tumours. We investigated the effectiveness of SDHB immunostaining as an initial screening tool in identifying SDH mutations.

This was a retrospective analysis of 23 randomly selected patients with PCC (10) and PGL (13); all benign lesions who were referred for genetic testing. Age (41 years, mean, range 15–69), 12 M and 12 F. Ten patients had PCC of which six were left sided and one bilateral. Abdominal and head and neck PGLs were present in seven patients each and thoracic PGLs in two. SDHB immunostaining was performed on all tumour samples using Sigma prestige antibodies (HPA 002868 100 U/l – anti-SDHB rabbit MAB) at a dilution of 1:1000. Staining was done using Leica BOND-III IHC stainer at ERZ (high pH) for 30 min. In PCC, 70% of the tumours were sporadic and RET, VHL, and SDHC–variants of unknown significance (VUS) contributed the rest (10% each). In the PGL group, 15% were sporadic, SDH mutations accounted for 38% and the rest, VUS. Immunostaining was found to be negative in the tumour sample of all patients with SDHB mutations and one SDHD, weakly positive with diffuse cytoplasmic blush in two SDHD and strongly positive in all sporadic, RET, VHL, and VUS mutations.

Our pilot data from a large cohort (~150 patients) indicate that SDHB immunostaining can reliably predict SDH mutational status and adds value in characterising patients with VUS.