To evaluate the expression profile of succinate dehydrogenase (SDH)B and SDHC in pheochromocytoma (PCC) and paraganglioma(PGL) (collectively abbreviated as PPGL), and their value in the early diagnosis of malignancy.

SDHB and SDHC immunohistochemistry were performed on 140 tumor specimens from 126 PPGL patients (PCC n=62, PGL n=61, PCC+ PGL n=3).

(1) Germline mutation status of 67 patients were determined, of which, identifying 37(55.2%) patients with germline mutation: 2 (3.0%) SDHA, 18 (26.9%) SDHB, 2 (3.0%) SDHC, 5 (7.5%) SDHD, 2 (3.0%)VHL, 7 (10.4%) RET, and 1(1.5%) NF1; and 30 (44.8%) individuals without known mutation. (2) Among 30 PPGLs from 27 patients with SDH-related (SDHx) mutations, 96.7% (29/30) stained negative for SDHB, 76.7% (23/30) stained negative for SDHC, while only 28.6% (14/49) and 18.4% (9/49) stained negative for SDHB and SDHC respectively in the 49 PPGLs without SDHx mutation (P<0.05). (3) The sensitivity of the SDH immunostaining in detecting the presence of germline SDHx mutation was 96.7% for SDHB and 76.7% for SDHC, while the specificity was 71.4% for SDHB and 81.6% for SDHC. (4) Among PPGLs without SDHB expression, 22.9% were malignant. This percentage is significantly higher than that in PPGLs with preserved SDHB expression (3.8%, P<0.05).

SDHB and SDHC immunohistochemistry may serve as post-surgical screening tools to predict the presence of germline SDHx mutation in PPGLs. Negative SDHB expression calls for intense follow-up to rule out malignancy. (Chin J Endocrinol Metab, 2018, 34: 472-478)

Succinate dehydrogenase; Immunohistochemistry; Pheochromocytoma; Paraganglioma