Expression of Kit and platelet-derived growth factor receptors alpha and beta in cholangiocarcinoma, and case report of therapy with imatinib mesylate (STI571).
We have evaluated the expression of Kit, a receptor encoded by the c-kit protooncogene, and platelet-derived growth factor-receptors (PDGF-R) alpha and beta in cholangiocarcinoma specimens from 13 separate patients, and provide a case report of a therapeutic trial of imatinib mesylate in one patient. Archived pathologic samples from 13 patients with cholangiocarcinoma were obtained. Tissue sections were hybridized with anti-Kit, anti-PDGF-Ralpha and anti-PDGF-Rbeta monoclonal antibodies. Kit, PDGF-Ralpha and PDGF-Rbeta expression was seen in 31, 69 and 46% of samples, respectively. All patients with PDGF-Rbeta expression also expressed PDGF-Ralpha. Three out of four patients with Kit expression did not express either PDGF receptor and only one patient exhibiting expression of PDGF expressed Kit. Cohen's kappa statistic demonstrated that PDGF and Kit expression were inversely correlated with borderline significance (p=0.052; kappa=-0.4742, 95% confidence interval -0.9821 to 0.03364). In one case, strong Kit expression was noted in a tumor from a metastatic lymph node, but was absent in the primary tumor, suggesting that Kit may be related to invasive or metastatic potential. Given the high level of expression defined in this study, a prospective clinical trial incorporating imatinib mesylate, alone or in combination with cytotoxic chemotherapy, and especially in chemotherapy-naive patients, should be considered for patients with cholangiocarcinoma.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta