Well-differentiated pancreatic ductal adenocarcinomas measuring ≤ 1 cm exhibit early features of tumor progression: a report of five lesions and a comparative study with advanced lesions

Surg Today. 2014 Nov;44(11):2058-64. doi: 10.1007/s00595-013-0804-1. Epub 2013 Dec 3.

Abstract

Purpose: The purpose of this study was to clarify whether the features of well-differentiated pancreatic ductal adenocarcinomas (PDACs) measuring ≤ 1 cm are the same as those of early PDACs.

Methods: Five well-differentiated PDACs measuring ≤ 1 cm were clinicopathologically compared with 19 ≥ 2 cm PDACs. Additionally, an immunohistochemical analysis for abnormalities in the expression of five molecular parameters: MUC1, p16, p53, Smad4 and sonic hedgehog, which are associated with tumor progression, was performed.

Results: The clinicopathological comparison revealed that well-differentiated PDACs measuring ≤ 1 cm were detected significantly more often without angiolymphatic invasion and with a sparse presence of cancer cells than were the ≥ 2 cm PDACs. On the other hand, in well-differentiated PDACs measuring ≤ 1 cm, the incidence of abnormal immunolabeling for MUC1, p16, p53 and sonic hedgehog was similar to that in ≥ 2 cm PDACs. However, the incidence of diffusely positive immunolabeling for MUC1 and the mean number of abnormally immunolabeled samples for the five parameters were significantly lower in well-differentiated ≤ 1 cm PDACs (20 % and 3 ± 1) than in ≥ 2 cm PDACs (90 % and 4 ± 1).

Conclusion: The current study revealed that as the tumor size increases, molecular abnormalities are accumulated, suggesting that well-differentiated PDACs measuring ≤ 1 cm are in an earlier stage of genetic progression than are ≥ 2 cm PDACs, and these lesions may exhibit early features of invasive PDACs.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Disease Progression
  • Female
  • Gene Expression
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Hedgehog Proteins
  • MUC1 protein, human
  • Mucin-1
  • Neoplasm Proteins
  • SHH protein, human
  • Tumor Suppressor Protein p53