c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: incidence, mechanisms, and clinical significance

Mod Pathol. 2002 Apr;15(4):462-9. doi: 10.1038/modpathol.3880547.


Amplification and overexpression of c-MYC is a common event in various neoplasias. Recently, comparative genomic hybridization (CGH) of primary pancreatic adenocarcinomas revealed a distinct high-level amplification of 8q23-qter, suggesting that c-MYC located on 8q24 may be a candidate oncogene. To evaluate the biological significance and prognostic value of c-MYC activation in pancreatic carcinoma, we performed interphase fluorescence in situ hybridization (FISH) and immunohistochemistry on a series of 69 primary pancreatic adenocarcinomas, 19 corresponding lymph node metastases, and 5 pancreatic intraductal lesions. Dual color FISH using a probe for c-MYC (8q24) and a centromeric probe for chromosome 8 revealed amplification of c-MYC in 32.3% and 29.4% of primary and metastatic tumors, respectively. Immunostaining identified c-MYC protein overexpression in 43.5% of primaries and 31.6% of metastases. Low concordance between positive FISH and immunostaining (13.4%) suggests multiple independent regulatory pathways of c-MYC activation. Statistical evaluation revealed significant correlation (alpha = 0.033) between c-MYC protein overexpression and histopathological tumor grade but absence of correlation with tumor stage or lymph node status. Analysis of pancreatic intraductal lesions showed c-MYC amplification and protein overexpression in two of five cases in which invasive carcinoma exhibited identical aberrations. We conclude that deregulation of c-MYC protein is common in pancreatic cancer and that it may be involved in early neoplastic development and progression rather than in locoregional spread of invasive cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Data Interpretation, Statistical
  • Gene Amplification
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics*


  • Proto-Oncogene Proteins c-myc