Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma

Objective. Our objective was to determine whether cytokinetic and molecular analyses of curettage specimens can provide a mechanism for triage of pati ents with endometrial cancer before initiating definitive surgical treatmen t. Methods. Pretreatment analysis consisted of how cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohis tochemical determination of expression of proliferating cell nuclear antige n, HER-2/neu, and p53 in curettage specimens from 134 patients with endomet rial carcinoma who subsequently had surgical staging and definitive surgica l treatment. Fisher's exact test or chi(2) was used to examine the associat ion between pretreatment variables and traditional surgical-pathologic indi ces. The log-rank test was used for univariate survival analysis. Cox propo rtional hazards identified the most important molecular factors. Results. Nondiploid status, SPF greater than or equal to 9%, and PI greater than or equal to 14% were associated with the traditional posttreatment pr ognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF greater than or equal to 9%, PI greater than or equal to 14%, and p53 overexpressi on and decreased progression-free survival (PFS) and disease-related surviv al (DRS). Stepwise Cox regression analysis identified p53 overexpression an d SPF greater than or equal to 9% as the most significant pretreatment mole cular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that wh en both factors are present the risk for recurrence was higher (RR = 7.07; 95% confidence interval [CI], 3.06-16.38; P < 0.01) and death due to diseas e was higher (RR = 9.93; 95% CI, 3.92-25.19; P < 0.01) than when no factors are present. In the group with both factors, 5-year PFS and DRS estimates were 41 and 44%, respectively, compared with 86 and 86% and 90 and 92% for the "none" and "one" groups, respectively. Conclusion. When observed simultaneously, increased SPF and p53 overexpress ion defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens cou ld provide a mechanism of triage that could be applied before definitive su rgical treatment. (C) 2000 Academic Press.