Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma

Anticancer Res. 2017 Aug;37(8):4529-4537. doi: 10.21873/anticanres.11850.


Aim: Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis.

Materials and methods: The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas.

Results: Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74.36% and 69.23%.

Conclusion: BNEC is one of the most malignant tumors with severe invasiveness and poor prognosis. Immunohistochemistry revealed that CD56, Syn, CgA, NSE, TTF-1, CK, CK7, CK20, P63, HMB45, S-100 protein and LCA immune markers play important roles in diagnosis and differentiation. Many factors, including the patient's age, size and shape of the tumor, operative method, perineuronal invasion, vascular invasion, distant organ metastasis and pathological type, show great difference in influencing OS time of patients, among which the size of the tumor, no invasion, vascular invasion and distant organ metastasis are independent risk factors affecting prognosis (survival time). Radical cystectomy is the prior alternative to treat this tumor.

Keywords: Bladder; NEC; immunohistochemistry; pathological features.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Biopsy
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / mortality*
  • Carcinoma, Neuroendocrine / pathology*
  • Carcinoma, Neuroendocrine / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phenotype
  • Prognosis
  • Risk Factors
  • Sex Factors
  • Tumor Burden
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / therapy


  • Biomarkers