Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

Br J Cancer. 2019 Apr;120(7):697-702. doi: 10.1038/s41416-019-0415-8. Epub 2019 Mar 6.

Abstract

Background: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies.

Methods: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score.

Results: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival.

Conclusions: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / classification
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenomatous Polyposis Coli Protein / genetics
  • Ampulla of Vater*
  • CDX2 Transcription Factor / metabolism
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Common Bile Duct Neoplasms / classification
  • Common Bile Duct Neoplasms / genetics*
  • Common Bile Duct Neoplasms / metabolism
  • Common Bile Duct Neoplasms / pathology
  • Duodenal Neoplasms / classification
  • Duodenal Neoplasms / genetics*
  • Duodenal Neoplasms / metabolism
  • Duodenal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Keratin-20 / metabolism
  • Keratin-7 / metabolism
  • Male
  • Middle Aged
  • Mucin 5AC / metabolism
  • Mucin-1 / metabolism
  • Mucin-2 / metabolism
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / genetics

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • KRAS protein, human
  • Keratin-20
  • Keratin-7
  • MUC1 protein, human
  • MUC2 protein, human
  • MUC5AC protein, human
  • Mucin 5AC
  • Mucin-1
  • Mucin-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins p21(ras)