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 patients with endometrial cancer before initiating definitive surgical treatment.


METHODS
Pretreatment analysis consisted of flow cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohistochemical determination of expression of proliferating cell nuclear antigen, HER-2/neu, and p53 in curettage specimens from 134 patients with endometrial carcinoma who subsequently had surgical staging and definitive surgical treatment. Fisher's exact test or chi(2) was used to examine the association between pretreatment variables and traditional surgical-pathologic indices. The log-rank test was used for univariate survival analysis. Cox proportional hazards identified the most important molecular factors.


RESULTS
Nondiploid status, SPF >/=9%, and PI >/=14% were associated with the traditional posttreatment prognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF >/=9%, PI >/=14%, and p53 overexpression and decreased progression-free survival (PFS) and disease-related survival (DRS). Stepwise Cox regression analysis identified p53 overexpression and SPF >/=9% as the most significant pretreatment molecular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that when 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 disease 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.


CONCLUSIONS
When observed simultaneously, increased SPF and p53 overexpression defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens could provide a mechanism of triage that could be applied before definitive surgical treatment.
Silverman
M B
MB
Department of Obstetrics and Gynecology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Roche
P C
PC
Kho
R M
RM
Keeney
G L
GL
Li
H
H
Podratz
K C
KC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology*; D003475:Curettage; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods*; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D018570:Risk Assessment; D016196:S Phase; D016019:Survival Analysis; D014218:Triage; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53