Endometrial stromal sarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 17 cases

Seventeen patients with endometrial stromal sarcoma (ESS) diagnosed between 1970 and 1996 were evaluated according to DNA ploidy, S-phase fraction (SP F), p53, and mdm-2 expression, as well as traditional clinical and patholog ic prognostic factors, such as tumor stage, grade, and mitotic index. DNA f low cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors . Flow cytometric DNA histograms were obtained from 16 patients. The patients ranged in age from 41 to 78 years (median, 57 years). Seven (4 1%) patients were premenopausal. Thirteen low-grade ESS were DNA diploid an d had a low SPF. Of these, two overexpressed p53, while only one was mdm-2 positive. Among the four high-grade ESS we found one (25%) DNA diploid tumo r and three (75%) DNA aneuploid tumors. Two (50%) had an SPF greater than 1 0%, three (75%) were p53-positive, and two (50%) overexpressed mdm-2. Durin g the observation period, nine (53%) patients (five with low-grade and four with high-grade tumors) died of disease. The 5-year survival rate for pati ents with low-grade ESS was 74%, while all four patients with high-grade ES S died of disease within 14 months of diagnosis. Using the log-rank test, w e found a significant correlation between survival and tumor grade (P = 0.0 07), DNA ploidy (P = 0.026), SPF (P = 0.048), and FIGO surgical stage (P = 0.026). In conclusion, we found that tumor grade was a strong predictor of clinical outcome in ESS. In addition, a worse prognosis was found for those ESS patients with advanc ed disease, DNA aneuploidy, and a high SPF. There was no difference between the recurrent and nonrecurrent group of early stage (surgical stage I), lo w-grade ESS with regard to clinicopathological features, DNA ploidy, SPF, p 53, and mdm-2 expression. All patients with high-grade ESS died of disease within 14 months of diagnosis. In contrast, only three of the 11 patients w ith early stage, low-grade ESS died of disease.