Immunohistochemical validation of a novel epithelial and a novel stromal marker of pancreatic ductal adenocarcinoma identified by global expression microarrays: sea urchin fascin homolog and heat shock protein 47

Am J Clin Pathol. 2002 Jul;118(1):52-9. doi: 10.1309/3PAM-P5WL-2LV0-R4EG.

Abstract

We extended the results of a previous microarray analysis by immunohistochemical validation of differential protein expression in a series of 57 surgically resected infiltrating ductal pancreatic adenocarcinomas. Two representative genes were examined: sea urchin fascin homolog (overexpressed in both cell lines and primary tumors) and heat shock protein 47 (HSP47; overexpressed in primary tumors only). Protein expression also was evaluated in the precursor lesions of pancreatic cancer pancreatic intraepithelial neoplasia (PanIN), and normal ductal epithelium. Fascin expression was seen in the neoplastic cells of 54 (95%) of 57 ductal adenocarcinomas but not in 49 (94%) of 52 adjacent nonneoplastic epithelium. In the multistep pathogenesis of ductal adenocarcinomas, fascin expression seemed to be a late event, usually present in PanINs 2 and 3. HSP47 expression was almost universal and most intense in the ductal adenocarcinoma-associated stromal desmoplasia (57/57), although 37 cases (65%) also expressed HSP47 in the neoplastic epithelium. HSP47 expression was absent in the majority of nonneoplastic pancreata (46 [88%]). Fascin and HSP47 are novel tumor markers with potential diagnostic and therapeutic implications for pancreatic carcinoma. These results establish the usefulness of global expression platforms to identify novel tumor markers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / genetics
  • Carcinoma in Situ / genetics*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / secondary
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Count
  • Female
  • Gene Expression
  • Gene Expression Profiling*
  • HSP47 Heat-Shock Proteins
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA, Neoplasm / analysis
  • Sea Urchins

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • HSP47 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Microfilament Proteins
  • RNA, Neoplasm
  • SERPINH1 protein, human
  • fascin