K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient.
Mutations involving the K-ras proto-oncogene are believed to play an important role in the mechanism of tumorigenesis for many human cancers and occur in 10-30% of endometrial carcinomas. In the present study 221 cases of endometrioid endometrial carcinoma obtained from Japanese patients with average follow-up of 41 months were examined for point mutations in codon 12 of K-ras through use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-ras mutations were significantly associated with the presence of lymph node metastases (P < 0.04). Since endometrial carcinoma in premenopausal women generally behaves less aggressively than tumors of similar histologic grade arising in postmenopausal patients, we evaluated the effect of K-ras mutation on outcome in patients stratified into three different age categories (<53 years, premenopausal; 54-59 years, perimenopausal; >60 years, postmenopausal). In the postmenopausal age group (>60 years), the presence of K-ras mutations was statistically significantly associated with patients who died or experienced recurrence (41.2% vs 13.0%; P < 0.03). This was related to a dramatic (greater than eightfold; P = 0.011) increase in the likelihood of adverse outcome between the premenopausal and postmenopausal states for patients whose tumors contained mutant K-ras. These findings point to a possible role for K-ras activation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
K
K
Ito
K
K
Watanabe
S
S
Nasim
H
H
Sasano
S
S
Sato
A
A
Yajima
S G
SG
Silverberg
C T
CT
Garrett
D000328:Adult; D000367:Age Factors; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D003062:Codon / Q000235:genetics*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas
D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas