K-rasPoint Mutations in Endometrial Carcinoma: Effect on Outcome Is Dependent on Age of Patient

Mutations involving the K-rasproto-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-rasthrough use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-rasmutations 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-rasmutation 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-rasmutations 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-rasactivation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.