DNA Defects Predict Endometrial Ca Prognosis

August 1, 1995

SAN FRANCISCO--A retrospective study of 61 endometrial cancers, collected from patients at the City of Hope Hospital, Duarte, Calif, found that approximately 49% of the tumors had some type of DNA abnormality, Kristi Van Nostrand, MD, reported at the American College of Obstetricians and Gynecologists (ACOG) annual clinical meeting.

SAN FRANCISCO--A retrospective study of 61 endometrial cancers,collected from patients at the City of Hope Hospital, Duarte,Calif, found that approximately 49% of the tumors had some typeof DNA abnormality, Kristi Van Nostrand, MD, reported at the AmericanCollege of Obstetricians and Gynecologists (ACOG) annual clinicalmeeting.

The 5-year survival rate for the entire cohort was 83%. The mostcommon mutations were c-myc amplification and p53 mutations, andpatients with these tumors had the poorest survival rates.

K-ras mutations and HER-2/neu amplification were the next mostcommon, and those patients with HER-2/neu amplification had abetter survival rate than the rest of the group.

"A lot of studies have looked at a variety of these mutations,but none has looked for all four of the most common mutationsat the same time," said Dr. Van Nostrand, a gynecology/oncologyfellow at the University of California at Irvine.

The California researchers found that HER-2/neu and K-ras abnormalitiestended to be seen in low-grade, low-stage tumors, leading themto believe that they are early occurrences in tumorigenicity.The c-myc and p53 abnormalities were seen in higher-grade, higher-stage,poor prognosis tumors.

Overall, the patients with abnormalities tended to he older, butthere were significant differences among patients with differentabnormalities. On average, patients with K-ras mutations wereolder, while those with HER-2/neu amplification tended to be younger.

The researchers found five tumors that had more than one mutation,Dr. Van Nostrand reported. The patients with these tumors hada comparable, if not better, survival rate than the other patients.Thus, it appears that progressive accumulation of these differentmutations does not add up to poor prognostic tumors, she said.The majority of the tumors with more than one mutation had p53mutations, and HER-2/neu was the abnormality most often associatedwith another mutation.

Since c-myc and p53 are often present in poor prognostic tumors,they may be useful postsurgery indicators of a patient's riskof recurrence, she said. Such patients would be candidates forpostoperative therapies, including radiation and chemotherapy.

Dr. Van Nostrand noted that researchers are currently trying toalter these mutations via gene therapy. "It will be veryinteresting to see if the biology of tumorigenic cells can bereversed," she said.