Molecular and histopathologic predictors of distant failures in corpus cancer

A Mariani, MD, TJ Sebo, MD, PhD, J Katzman, PhD, D Riehle, GL Keeney, MD, KC Podratz, MD, PhD

Mayo Clinic, Rochester, MN United States

Aim: Correlation of various histopathologic and molecular variables with distant failures in endometrial cancer. Patients and Methods: A case-cohort designed study was used to select 125 patients from an overall endometrial cancer population of 283 patients for analysis of phenotypic and molecular indices in hysterectomy specimens. The case-cohort included all patients (n=49) experiencing a recurrence as well as randomly chosen progression-free patients (n=76). Expression of nuclear PCNA, MIB-1 and p53 was determined via Digital Image Analysis and cytoplasmic HER-2/neu and bcl-2 was visually quantitated. Ploidy and various DNA indices were determined by Flow Cytometry. We defined distant failures as primary recurrences that developed outside the pelvis/vagina. Median follow-up of surviving patients was 92 months. Weighted statistics with chi-square test and logistic regression analysis were used correlating indices and distant failures. Results: Distant failures were observed in 13% of the patients in the reference population. Cervical stromal invasion, adnexal involvement, myometrial invasion >50%, lymph node metastasis, positive peritoneal cytology, lymph vascular invasion, grade 3 histology, non-endometrioid subtype, p53 >033%, HER-2/neu overexpression, aneuploidy, S-phase fraction greater or equal to 9%, Proliferative Index greater or equal to 14%, and DNA Index greater or equal to 1.5 significantly predicted distant failures (p<0.05). However, a logistic regression model identified only p53 (OR=41.76; p<0.01), lymph vascular invasion (OR=10.50; p<0.01) and cervical stromal invasion (OR=9.95; p<0.01) as cogent predictors of distant failures. In the absence of any of the above 3 variables only 3% of patients developed distant failures, compared to 36% of patients in whom at least one of the above 3 factors was positive (p<0.01). Conclusion: Presence of p53 >33%, LVI and CSI were independent predictors of distant failures in endometrial cancer. These observations would suggest that locoregional therapy is insufficient to definitively manage patients when at least one of the above indicators of distant failure is positive.

KEY WORDS: phenotypic and biological indices, endometrial cancer, predictors of recurrence.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.