Genetic alterations in endometrial carcinomas

Endometrial cancer is the most common gynecologic malignancy Grade, lymph node status, and stage are known prognostic indicators and yet it is difficult to predict those patients at high risk for recurrence. To evaluate the prognostic value of a variety of oncogenes (K-ras, Her-2/neu, c-myc) and of p53 mutations, we studied 49 endometrial cancers using Southern blots, PCR/SSCP analysis, and PCR direct. sequencing. Chart review was performed to obtain clinical information (pathology, survival statistics). Statistical analysis was performed using log-rank, chi-square, and life table analysis. The mean age of the patients was 66 years. Overall, 26 tumors (53%) showed some form of oncogene alteration. Patients with alterations had a higher mean age (67) than those without (60). Patients with c-myc amplification (24%) had higher grade tumors and poorer 5-year survival (58%), although not significant statistically. Twenty-four percent of patients had p53 mutations, higher stage tumors, and poorer 5-year survival (54%). K-ras (6%) and HER-2/neu (8%) alterations were associated with lower grade tumors and, were not found to be prognostic indicators. Five patients had > 1 alteration. C-myc was found less frequently associated with other alterations than expected while HER-2/neu was found more frequently than expected. These results suggest that only 50% of endometrial cancers contain an alteration of these genes and that other alterations may exist and await identification. C-myc amplification and p53 mutations appear to be present in those patients with poorer prognosis; screening for these alterations may be useful in predicting those with a high risk for recurrence, thus allowing early adjuvant therapy.