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Original Article
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Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-β in ovarian serous carcinoma and normal ovarian surface epithelium
Article first published online: 25 JUN 2003
DOI: 10.1002/cncr.11561
Copyright © 2003 American Cancer Society
Additional Information
How to Cite
Schmandt, R. E., Broaddus, R., Lu, K. H., Shvartsman, H., Thornton, A., Malpica, A., Sun, C., Bodurka, D. C. and Gershenson, D. M. (2003), Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-β in ovarian serous carcinoma and normal ovarian surface epithelium. Cancer, 98: 758–764. doi: 10.1002/cncr.11561
Publication History
- Issue published online: 1 AUG 2003
- Article first published online: 25 JUN 2003
- Manuscript Accepted: 7 MAY 2003
- Manuscript Revised: 2 MAY 2003
- Manuscript Received: 24 JAN 2003
Funded by
- M. D. Anderson Blanton-David Ovarian Cancer Research Program
- Beth Liebman and the Elizabeth Fund
- Ovarian Cancer Research Fund
- Abstract
- Article
- References
- Cited By
Keywords:
- ovarian carcinoma;
- c-ABL;
- platelet-derived growth factor receptor;
- c-KIT;
- kinase inhibitor;
- immunohistochemistry
The immunohistochemical expression of c-ABL, platelet-derived growth factor receptor-β, and c-KIT tyrosine kinases was evaluated in ovarian serous carcinoma. The majority of serous epithelial ovarian tumors express one or more of these kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate.
Abstract
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. Cancer 2003;98:758–64. © 2003 American Cancer Society.
DOI 10.1002/cncr.11561