Racial Disparity in Overexpression of the P53 Tumor Suppressor Gene in Stage I Endometrial Cancer
Abstract & Commentary
Synopsis: Differences in the frequency of alteration of the p53 tumor suppressor gene appear to contribute to the racial disparity in endometrial cancer survival.
Source: Clifford SL, et al. Am J Obstet Gynecol 1997; 176:S229-232.
Clifford and colleagues conducted a study to determine whether overexpression of the p53 tumor suppressor gene is associated with poor outcome in early-stage endometrial cancers and whether a racial difference in the frequency of p53 overexpression contributes to the observed racial disparity in survival rates. Immunostaining for the p53 gene was performed in 164 women with stage I endometrial cancer. Overexpression of mutant p53 protein was seen in 28 of 164 (17%) cases and was associated with a poor histologic grade (P = 0.003) and a nonendometrioid histologic appearance (P = 0.06). Overexpression also was three times more frequent in blacks (15 of 44; 34%) than in whites (13 of 117; 11%) (P = 0.003). Recurrent disease developed in 15 of 164 (9%) cases and was more than twice as frequent in cases when the p53 gene was overexpressed (5 of 28; 18%) than in cases with normal expression (10 of 136; 7%). Recurrent disease was seen in six of 44 (14%) blacks compared to nine of 117 (8%) whites. Clifford et al conclude that the data from this study support the hypothesis that differences in the frequency of alteration of the p53 tumor suppressor gene contribute to the racial disparity in endometrial cancer survival.
COMMENT BY DAVID M. GERSHENSON, MD
As pointed out by Clifford et al, the incidence of endometrial cancer in blacks (14.8 per 100,000) is lower than that in whites (22.3 per 100,000), but the five-year survival rate of blacks is only 60% compared with 90% for whites. There are several potential reasons for this disparity in survival, including less frequent use of estrogen replacement therapy in blacks, delayed diagnosis related to inadequate access to medical care, and different biological factors. This paper focuses on the molecular biological factors, specifically the p53 tumor suppressor gene. A previous study by this group revealed that mutant p53 was overexpressed in 9% of endometrial cancers confined to the uterus and in 41% of cases of metastatic endometrial cancer.
Overexpression of mutant p53 is also associated with other unfavorable prognostic features, including high- grade and papillary serous histology. Several other studies have also suggested that overexpression of mutant p53 in early-stage endometrial cancer is associated with a worse prognosis. In this study, blacks did have a higher incidence of high grade and nonendometrioid histology than whites. Although it did not quite achieve statistical significance, only 8% of black women had used hormones compared to 33% of white women.
In addition, although the recurrence rate was higher in blacks (14% vs 8%), it did not reach statistical significance. This study adds to the evidence that overexpression of mutant p53 tumor suppressor gene in endometrial cancer is associated with unfavorable outcome. Clearly, this molecular alteration contributes to poor outcome in blacks but is probably only partially responsible for the observed outcome.
Studies by the Duke group have significantly enhanced our understanding of the biological behavior of endometrial cancer, and I look forward to further work in this area.
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