Elsevier

Human Pathology

Volume 32, Issue 11, November 2001, Pages 1184-1189
Human Pathology

Original Contributions
Immunohistochemical expression of transforming growth factor α and epidermal growth factor receptor in pancreatic endocrine tumors*

https://doi.org/10.1053/hupa.2001.28959Get rights and content

Abstract

Coexpression of transforming growth factor α (TGF-α) 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-α, 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-α; and 23 (65%) were positive for the intracellular and/or extracellular domain of EGFR. Based on their TGF-α and EGFR expression, these tumors could be classified into 4 groups. Of the 10 tumors in group I (positive for TGF-α 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-α 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-α and EGFR) included 4 malignant tumors, 3 PETs >2 cm in diameter, and 4 functional lesions. Therefore, immunohistochemical expression of TGF-α 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. HUM PATHOL 32:1184-1189. Copyright © 2001 by W.B. Saunders Company

Section snippets

Materials and methods

Thirty-five PETs (21 benign and 14 malignant) were retrieved from the surgical pathology files of the New England Medical Center for the study. All original hematoxylin and eosin (H & E)–stained slides on each of these cases were reviewed to confirm the diagnosis and to select representative paraffin blocks with tissues adequate enough to yield 30 to 35 serial sections. Metastatic lesions were included for study only if sufficient tissue material was available on both the primary tumor and the

Results

The 21 benign and 14 malignant PETs included in the study were obtained from 10 male and 25 female patients ranging in age from 11 to 76 years. Twenty tumors were associated with a functional syndrome and could be categorized as insulinoma (n = 10), gastrinoma (n = 7), VIPoma (n = 2), and GHRF-producing tumors (n = 1) based on the dominant secretory product (see below). The other 15 tumors were clinically nonfunctional. The 14 malignant tumors (with demonstrable metastases) varied in size from

Discussion

Cellular growth and/or differentiation is normally initiated when extracellular growth factors bind with their specific transmembrane receptors and send a physical signal through the cell membrane. Inside the cell, this signal is propagated by activation of an enzyme, usually a tyrosine-specific kinase that is either intrinsic to or closely associated with the cytoplasmic face of the receptor.25, 26 A variety of different intracellular proteins then carry the signal to the nucleus, where

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    *

    Address correspondence and reprint requests to Yogeshwar Dayal, MD, Department of Pathology, New England Medical Center, 750 Washington St, Boston, MA 02111.

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