Loss of succinate dehydrogenase subunit B (SDHB) as a prognostic factor in advanced ileal well-differentiated neuroendocrine tumors

Endocrine. 2017 Sep;57(3):512-517. doi: 10.1007/s12020-016-1180-6. Epub 2016 Nov 30.


Purpose: Abnormal expression of succinate dehydrogenase, (SDH), in particular of the B subunit (SDHB), is implicated in the pathogenesis of neuroendocrine tumors. This study evaluates the distribution of SDHB in WHO grading G1 and G2 intestinal, well-differentiated neuroendocrine tumors and corresponding lymph node or liver metastases.

Methods: We collected ileal well-differentiated neuroendocrine tumors specimens from consecutive patients with prior primary resection and distant synchronous or metachronous liver metastases. We obtained 195 specimens from primary tumors (n = 106) and metastases (n = 89). The expression (E) of SDHB and the immunostaining intensity (I) were evaluated semiquantitatively and combined into a single score. SDHB score was evaluated in primitive tumor and metastatic specimens.

Results: SDHB was found in all tumor cells. Mean SDHB expression was 72.7 % ± 17.1 % in primitive specimens and 27.9 % ± 24.6 % in metastatic specimens (p < 0.0001). SDH intensity was higher in primitive specimens (p < 0.0001). SDHB score was 9-12 in 96 specimens of the primitive group and 2 metastatic specimens (p < 0.0001). None of the analyzed parameters was predictive of overall survival in the primitive subset. In the metastatic subset, loss of SDHB expression, intensity, and score were prognostic factors for survival. Lower expression and intensity of SDHB in metastatic lesions were associated with longer overall survival. When combining SDHB score and Ki-67 % in the metastatic subset, a lower SDHB score was associated with prolonged overall survival, independently from Ki-67 %.

Conclusions: SDHB score was different in primitive and metastatic specimens. The combination of SDHB score and Ki-67 % was a stronger predictor of overall survival than Ki-67 % alone. This stratification might help predict survival.

Keywords: Ileal NET; Immunochemistry; Prognosis; SDHB.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Differentiation
  • Down-Regulation*
  • Female
  • Humans
  • Ileal Neoplasms / diagnosis
  • Ileal Neoplasms / metabolism*
  • Ileal Neoplasms / mortality
  • Ileal Neoplasms / pathology
  • Ileum / metabolism
  • Ileum / pathology
  • Liver / metabolism*
  • Liver / pathology
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / metabolism*
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / secondary
  • Prognosis
  • Succinate Dehydrogenase / metabolism*
  • Survival Analysis
  • Young Adult


  • Neoplasm Proteins
  • SDHB protein, human
  • Succinate Dehydrogenase