Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection

J Hepatobiliary Pancreat Sci. 2016 Aug;23(8):489-96. doi: 10.1002/jhbp.367. Epub 2016 Jul 3.

Abstract

Background: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC.

Methods: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated.

Results: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC.

Conclusions: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens.

Keywords: Ampulla of Vater; BNIP3; Carcinoma; Chemotherapy; Thymidylate synthase.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ampulla of Vater / pathology
  • Ampulla of Vater / surgery*
  • Biliary Tract Surgical Procedures / methods
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Common Bile Duct Neoplasms / drug therapy
  • Common Bile Duct Neoplasms / mortality
  • Common Bile Duct Neoplasms / pathology
  • Common Bile Duct Neoplasms / surgery*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Combinations
  • Female
  • Gemcitabine
  • Genes, bcl-2
  • Humans
  • Immunohistochemistry
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins / metabolism*
  • Rare Diseases
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis
  • Tegafur / administration & dosage
  • Thymidylate Synthase / metabolism*

Substances

  • BNIP3 protein, human
  • Biomarkers, Tumor
  • Drug Combinations
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Thymidylate Synthase
  • Gemcitabine