Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma

A. Schueneman, M. Goggins, J. Ensor, B. Saka, N. Neishaboori, S. Lee, A. Maitra, G. Varadhachary, N. Rezaee, C. Wolfgang, V. Adsay, H. Wang, M. J. Overman

Research output: Contribution to journalArticle

Abstract

Outcomes for ampullary adenocarcinomas are heterogeneous, and numerous methods of categorisation exist. A histomolecular phenotype based on histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We attempt to validate this classification in a large patient population.Methods:Tissue samples from 163 patients with resected ampullary adenocarcinoma were classified based on histology and immunohistochemical expression of CDX2 and MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a sample with pancreaticobiliary histology, positive MUC1 and negative CDX2 expression.Results:There were 82 deaths; median follow-up of 32.4 months; and median overall survival of 87.7 (95% CI 42.9-109.5) months. PB comprised 28.2% of the cases. Factors associated with overall survival were histological subtype (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT) vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was statistically significant, although MUC1 positivity defined as ≥10% staining was significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR 2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival.Conclusions:The prognostic ability of histomolecular phenotype has been validated in an independent cohort of ampullary adenocarcinoma patients.

Original languageEnglish (US)
Pages (from-to)64-68
Number of pages5
JournalBritish journal of cancer
Volume113
Issue number1
DOIs
StatePublished - Jun 30 2015

Keywords

  • Ampullary adenocarcinoma
  • CDX2
  • MUC1
  • histomolecular phenotype
  • prognostic

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schueneman, A., Goggins, M., Ensor, J., Saka, B., Neishaboori, N., Lee, S., Maitra, A., Varadhachary, G., Rezaee, N., Wolfgang, C., Adsay, V., Wang, H., & Overman, M. J. (2015). Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma. British journal of cancer, 113(1), 64-68. https://doi.org/10.1038/bjc.2015.172