Research presented recently at the Society of Gynecologic Oncologists (SGO) annual meeting found that survival rates of African-American women with advanced-stage endometrial cancers are significantly worse than those of Caucasian women.
Research presented recently at the Society of Gynecologic Oncologists (SGO) annual meeting found that survival rates of African-American women with advanced-stage endometrial cancers are significantly worse than those of Caucasian women. The median survival of African-Americans was 1 year, compared with 2½ years for Caucasians.
The study reviewed snap frozen-tissue samples or paraffin blocks of 140 women (78 Caucasian, 62 African-American) who underwent hysterectomy for endometrial adenocarcinoma between 1975 and 1997. The research was conducted by Andrew Berchuck, MD, G. Larry Maxwell, MD, Angeles A. Alvarez, MD, and Richard K. Dodge, PhD, from Duke University Medical Center; and John I. Risinger, PhD, and J. Carl Barrett, PhD, from the National Institute of Environmental Health Sciences.
Although African-American women have a lower incidence of endometrial cancer (14.6 per 100,000 population) than do Caucasian women (22.2 per 100,000), they have a significantly higher disease-related mortality. In a 1989-1994 review by the National Cancer Institute (NCI), the 5-year survival rate for all stages was 86% for Caucasian women vs only 54% for African-American women.
Although survival of African Americans is relatively poor for several types of cancer, the racial disparity is greatest for endometrial cancer, as seen in the Surveillance, Epidemiology and End Results (SEER) registry of the NCI. This disparity is attributable, in part, to the fact that African-American women, more often than their Caucasian counterparts, present with metastatic disease, thus significantly worsening their survival rates.
Differences in Molecular Pathogenesis
In a prior study by the Duke group, there was no racial disparity in the time from the onset of abnormal uterine bleeding to the diagnosis of endometrial cancer or in the intensity of treatment. This suggested that underlying racial differences in the molecular pathogenesis of the cancers might contribute to the disparity in survival. Consistent with this theory, it was subsequently shown that the racial disparity in survival can be attributed, in part, to a higher frequency in the overexpression of the p53 tumor-suppressor gene in African-Americansa molecular alteration associated with high-risk, nonendometrioid histology and poor prognosis.
Both mutation of the PTEN tumor suppressor gene and microsatellite instability are molecular changes that have been associated with favorable outcome in endometrial cancers. We needed to get a better understanding of any racial differences in the frequency of these molecular alterations to determine whether this contributes to the racial disparity in survival. Hopefully, if we can understand the molecular basis for the racial disparity in survival, we can use this knowledge to decrease the high mortality rate of African-American women with endometrial cancer, said the studys senior author Andrew Berchuck, md, professor, Department of Obstetrics and Gynecology, Duke University.
The study found no racial difference in the frequency of microsatellite instability in endometrial cancers, but mutations in the PTEN tumor-suppressor gene, which are associated with more favorable survival, were four times more common in endometrial cancers of Caucasians (22%) than in cancers of African-Americans (5%). This finding suggests that there are racial differences in the molecular pathways that lead to the development of endometrial cancer, and that these underlying differences in the molecular pathology contribute to the racial disparity in survival.
African-American women had cancers with significantly higher stage and grade that were more often nonendometrioid and overexpressed the p53 gene.
In 20/140 (14%) cancers, a PTEN mutation was seen. In addition, PTEN was associated with an endometrioid histology and more favorable survival.
The frequency of PTEN mutations was significantly higher in Caucasians (17/78, 22%) than in African-Americans (3/62, 5%). Mutations of the PTEN tumor-suppressor gene are associated with a favorable outcome.
Overexpression of p53 occurred much more frequently in African-Americans relative to Caucasians. Overexpression was three times more frequent in African-Americans than Caucasians with early-stage cancers (33% vs 11%) and two times more frequent in African-Americans with advanced-stage cancers (55% vs 25%).
n women with advanced-stage disease, survival of African-American women remained inferior to that of Caucasians even after controlling for p53 expression, suggesting that other molecular alterations also may contribute to racial differences in survival.
There was no racial difference in the frequency of microsatellite instability.