Annals of Oncology Advance Access originally published online on December 14, 2006
Annals of Oncology 2007 18(3):491-497; doi:10.1093/annonc/mdl455
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© 2006 European Society for Medical Oncology
gynecologic tumors |
RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer
1 Department of Obstetrics and Gynecology, Tweesteden Hospital, Tilburg
2 Research Institute Growth and Development (GROW)
3 Department of Obstetrics and Gynecology
4 Department of Pathology, University Hospital Maastricht, Maastricht
5 Department of Material Technology, Technical University Eindhoven, Eindhoven, The Netherlands
6 Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, USA
* Correspondence to: Dr J. M. A. Pijnenborg, Department of Obstetrics and Gynecology, Tweesteden Hospital, PO Box 90107, 5000 LA Tilburg, The Netherlands. Tel: +31-134655502; Fax: +31-134655501; E-mail: H.pijnenborg{at}planet.nl
Background: Aberrations in mediators of Ras signaling may increase the risk of developing recurrent endometrial carcinoma.
Patients and methods: Primary tumors of patients with (n = 44) and without (n = 44) recurrent stage I endometrioid endometrial carcinoma were compared regarding the presence of K-ras mutations (codons 12 and 13), B-raf mutations (V599), and RASSF1A gene promoter methylation.
Results: K-ras mutations were present in 18% of the patients independent of recurrent disease. No B-raf mutations were found. RASSF1A methylation was demonstrated in 85% of endometrial carcinomas, independent of recurrence. The presence of K-ras mutations and RASSF1A promoter methylation were not related, either directly or inversely. Analysis in premenopausal endometrial carcinomas demonstrated K-ras mutations in 40%, no B-raf mutations, and RASSF1A promoter methylation in 70% of the cases. RASSF1A methylation was also observed in samples of cyclic (n = 14), hyperplastic (n = 8), and atrophic (n = 13) endometrial tissues in 21%, 50% and 38%, respectively.
Conclusions: RASSF1A methylation was observed in a high frequency in endometrioid endometrial carcinoma whereas K-ras and B-raf mutations were observed in a low frequency. No association was observed with the development of recurrent disease. High-frequency RASSF1A methylation in premenopausal carcinomas and an increased frequency in endometrial hyperplasia indicate that this may be an early event in endometrial carcinogenesis.
Key words: B-raf, endometrial carcinoma, K-ras, mutation, RASSF1A
Received for publication September 1, 2005. Revision received October 17, 2006. Accepted for publication October 31, 2006.
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