Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors.
OBJECTIVE
Molecular targeting with monoclonal antibodies and tyrosine kinase inhibitors is a novel approach to cancer treatment. We have examined the expression of molecular targets in patients with malignant endocrine pancreatic tumors, which is necessary to justify additional studies investigating the potential benefit from such treatment.


METHODS
Thirty-eight tumor tissues from malignant endocrine pancreatic tumors were examined with immunohistochemistry using specific polyclonal antibodies with regard to the expression pattern of platelet-derived growth factor receptors (PDGFRs) alpha and beta, c-kit, and epidermal growth factor receptor (EGFR).


RESULTS
All 38 tissue specimens expressed PDGFRalpha on tumor cells, and 21 of 37 specimens (57%) expressed PDGFRalpha in tumor stroma (1 specimen was nonevaluable). Twenty-eight samples (74%) stained positive for PDGFRbeta on tumor cells, and 36 of 37 samples (97%) stained positive for PDGFRbeta in the stroma (1 specimen was nonevaluable). Thirty-five tumor tissues (92%) stained positive for c-kit, and 21 (55%) stained positive for EGFR on tumor cells. No differences were seen between syndromes or between poorly differentiated or well-differentiated tumors. Previous treatment did not influence expression pattern. Receptor expression pattern varied considerably between individuals.


CONCLUSIONS
We have found that tyrosine kinase receptors PDGFRs alpha and beta, EGFR, and c-kit are expressed in more than half of the patients with endocrine pancreatic tumors. Because these receptors represent molecular targets for STI571 and ZD1839 (tyrosine kinase inhibitors) and IMC-C225 (a monoclonal antibody), we propose that patients suffering from EPTs might benefit from this new treatment strategy. However, because of great variability in receptor expression pattern, all patients' individual receptor expression should be examined.
Fjällskog
Marie-Louise H
ML
Department of Medical Sciences, University Hospital, SE-751 85 Uppsala, Sweden. marie-louise.fjallskog@medsci.uu.se
Lejonklou
Margareta H
MH
Oberg
Kjell E
KE
Eriksson
Barbro K
BK
Janson
Eva T
ET
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002454:Cell Differentiation; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D053379:Chromogranin A; D002864:Chromogranins; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta