RASSF1A methylation and K-ras and B-raf mutations and recurrent endometrial cancer.
BACKGROUND
Aberrations in mediators of Ras signaling may increase the risk of developing recurrent endometrial carcinoma.


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.
Pijnenborg
J M A
JM
Department of Obstetrics and Gynecology, Tweesteden Hospital, Tilburg, The Netherlands. H.pijnenborg@planet.nl
Dam-de Veen
G C
GC
Kisters
N
N
Delvoux
B
B
van Engeland
M
M
Herman
J G
JG
Groothuis
P G
PG
D000328:Adult; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D004714:Endometrial Hyperplasia / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009426:Netherlands; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012042:Registries; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf