Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in pancreatic endocrine tumors.
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.
Srivastava
A
A
Department of Pathology, New England Medical Center, Boston, MA 02111, USA.
Alexander
J
J
Lomakin
I
I
Dayal
Y
Y
D007516:Adenoma, Islet Cell / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division; D002648:Child; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000276:immunology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D016211:Transforming Growth Factor alpha / Q000276:immunology / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D010187:Pancreatic Hormones; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors