Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in pancreatic endocrine tumors

Hum Pathol. 2001 Nov;32(11):1184-9. doi: 10.1053/hupa.2001.28959.

Abstract

Coexpression of transforming growth factor alpha (TGF-alpha) and its receptor epidermal growth factor receptor (EGFR) is known to be associated with aggressive biologic behavior and adverse clinical outcome in a variety of tumors, including pancreatic adenocarcinomas. However, very little information is currently available as to whether this is true of pancreatic endocrine tumors (PETs) as well. Thirty-five PETs were retrospectively studied for immunohistochemical expression of TGF-alpha, the intracellular and extracellular domains of EGFR, and various hormonal secretory products. Proliferative activity was additionally studied (in 20 cases only) using the MIB-1 antibody. Thirty-one (89%) of 35 tumors were reactive for 1 or more of the peptide hormones tested; 22 (63%) tumors were positive for TGF-alpha; and 23 (65%) were positive for the intracellular and/or extracellular domain of EGFR. Based on their TGF-alpha and EGFR expression, these tumors could be classified into 4 groups. Of the 10 tumors in group I (positive for TGF-alpha and the complete EGFR molecule), 3 were malignant, 6 were >2 cm in diameter, 5 were functional, and 1 had a proliferative index of >40%. The 12 tumors in group II (positive for TGF-alpha but negative for the intracellular and/or extracellular domain of EGFR) included 4 malignant tumors, 4 PETs >2 cm in diameter, 8 functional, and 1 with a proliferative index of >40%. The 7 PETs in group III (positive for the intracellular/extracellular domain of EGFR alone) included 3 malignant tumors, 3 PETs >2 cm in diameter, and 3 functional tumors. The 6 tumors in group IV (completely negative for both TGF-alpha and EGFR) included 4 malignant tumors, 3 PETs >2 cm in diameter, and 4 functional lesions. Therefore, immunohistochemical expression of TGF-alpha and EGFR, either alone or in concert, shows no correlation with size, functional status, secretory profile, or biologic behavior and hence cannot be used as a marker of malignancy in this group of tumors.

MeSH terms

  • Adenoma, Islet Cell / classification
  • Adenoma, Islet Cell / metabolism*
  • Adenoma, Islet Cell / pathology
  • Adolescent
  • Adult
  • Biomarkers, Tumor / analysis
  • Cell Division
  • Child
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / immunology
  • Male
  • Middle Aged
  • Pancreatic Hormones / immunology
  • Pancreatic Hormones / metabolism
  • Pancreatic Neoplasms / classification
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies
  • Transforming Growth Factor alpha / immunology
  • Transforming Growth Factor alpha / metabolism*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Pancreatic Hormones
  • Transforming Growth Factor alpha
  • ErbB Receptors