TY - JOUR
T1 - Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-β in ovarian serous carcinoma and normal ovarian surface epithelium
AU - Schmandt, Rosemarie E.
AU - Broaddus, Russell
AU - Lu, Karen H.
AU - Shvartsman, Hyun
AU - Thornton, Angela
AU - Malpica, Anais
AU - Sun, Charlotte
AU - Bodurka, Diane C.
AU - Gershenson, David M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/8/15
Y1 - 2003/8/15
N2 - BACKGROUND. Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-β), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-β, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. METHODS. The expression of c-ABL c-KIT, and PDGFR-β in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. RESULTS. In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-β was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-β expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. CONCLUSIONS. The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma.
AB - BACKGROUND. Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-β), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-β, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. METHODS. The expression of c-ABL c-KIT, and PDGFR-β in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. RESULTS. In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-β was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-β expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. CONCLUSIONS. The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma.
KW - C-ABL
KW - C-KIT
KW - Immunohistochemistry
KW - Kinase inhibitor
KW - Ovarian carcinoma
KW - Platelet-derived growth factor receptor
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U2 - 10.1002/cncr.11561
DO - 10.1002/cncr.11561
M3 - Article
C2 - 12910520
AN - SCOPUS:0041570242
SN - 0008-543X
VL - 98
SP - 758
EP - 764
JO - Cancer
JF - Cancer
IS - 4
ER -