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.
Ito
K
K
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
Watanabe
K
K
Nasim
S
S
Sasano
H
H
Sato
S
S
Yajima
A
A
Silverberg
S G
SG
Garrett
C T
CT
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