Prognostic impact of neuroendocrine differentiation in high-grade serous ovarian carcinoma

Virchows Arch. 2015 Mar;466(3):333-42. doi: 10.1007/s00428-014-1710-7. Epub 2014 Dec 19.


Neuroendocrine differentiation in high-grade serous ovarian carcinomas has only rarely been described. However, in our consultancy experience, we have been pointed at a case of neuroendocrine relapse in a patient with high-grade serous ovarian carcinoma where retrospectively, a minor neuroendocrine component in the primary tumor could be detected. Hypothesizing that immunohistochemical evidence of neuroendocrine differentiation might be more frequent in ovarian carcinoma than suspected by morphology, we immunophenotyped the tissue microarrays (TMAs) of a cohort of 178 high-grade serous carcinomas for chromogranin and synaptophysin expression. Synaptophysin expression was found in 12 (6.7 %) out of 172 patients, and chromogranin A expression was seen in 36 (20.7 %) out of 174 patients. Kaplan-Meier analysis revealed that carcinomas with synaptophysin expression of >20 % of positive cells (n = 4) had a significantly shorter survival time than those with 0-20 % of positive cells (p < 0.0001). Synaptophysin expression remained a significant prognostic factor in multivariate analysis (HR = 10.82, 95 % confidence interval 3.10-37.71, p < 0.0001), independently of age, FIGO stage, and residual tumor after surgery. A trend toward shorter survival was seen in patients with tumors that expressed chromogranin, irrespective of the amount of positive cells (p = 0.173). A neuroendocrine differentiation is important to keep in mind when a neuroendocrine tumor of unknown primary is detected in regional or temporal connection with an ovarian carcinoma. A minor neuroendocrine component in ovarian high-grade serous carcinomas might imply a dismal prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Cell Differentiation
  • Chromogranins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasms, Cystic, Mucinous, and Serous / diagnosis
  • Neoplasms, Cystic, Mucinous, and Serous / metabolism
  • Neoplasms, Cystic, Mucinous, and Serous / pathology*
  • Neurosecretory Systems / pathology*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Retrospective Studies
  • Synaptophysin / metabolism


  • Biomarkers, Tumor
  • Chromogranins
  • Synaptophysin