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Prospective Multicenter Validation Confirms the Prognostic Superiority of the Endometrial Carcinoma Prognostic Index in International Federation of Gynecology and Obstetrics Stage 1 and 2 Endometrial Carcinoma

Jan P.A. Baak, Wim Snijders, Bianca van Diermen, Paul J. van Diest, Fred W. Diepenhorst, Jantine Benraadt

From the Department of Pathology, Rogaland Central Hospital, Stavanger, Norway; Vrije Universiteit; Vrije Universiteit Medical Center; Comprehensive Cancer Center Amsterdam, Amsterdam; and Department of Gynecology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands.

Address reprint requests to Jan P.A. Baak, MD, PhD, Department of Pathology, Rogaland Central Hospital, PO Box 8100, 4068 Stavanger, Norway; e-mail: baja{at}sir.no.

Purpose: To validate the prognostic value of the endometrial carcinoma prognostic index (ECPI; combined myometrium invasion, flow cytometric DNA ploidy, and morphometric mean shortest nuclear axis [MSNA]) versus classic prognosticators.

Patients and Methods: Prospective multicenter ECPI analysis was conducted in 463 endometrial carcinomas with a median of 6.5 years (range, 1 to 10 years) follow-up, review of pathology features, and univariate (Kaplan-Meier) and multivariate (Cox) analyses.

Results: Initial routine and review diagnoses varied considerably (invasion depth, 11%; type, 20%; grade, 34%; vessel invasion, 72%); the review diagnoses were stronger prognostically. In International Federation of Gynecology and Obstetrics stage 1 (after histopathologic examination; pFIGO-1; n = 372; 38 deaths occurred as a result of disease [10.2%]), DNA ploidy was prognostic in hysterectomies (P < .00001) but not in curettages (P = .06). ECPI was a stronger prognostic indicator than other features. ECPI, MSNA, and DNA ploidy were also prognostic in pFIGO-1B and -1C subgroups. Multivariate analysis in pFIGO-1 showed that uterine MSNA versus > 7.93 µm (hazard ratio [HR], 3.4) and grade (as 1 + 2 v 3; HR, 2.6) added to the ECPI (HR, 32), but only in patients with an unfavorable ECPI of > 0.87. Adjuvant radiotherapy was not an independent prognostic factor in any of the subgroups. In pFIGO-2 (n = 46), ECPI, DNA-ploidy, and age ( 64, > 64 years) were significant. In FIGO-3 (n = 31) and FIGO-4 (n = 14), none of the classic or other features analyzed was of prognostic value, which explains why in previous studies using different mixtures of FIGO stages, DNA ploidy prognostic results varied.

Conclusion: In endometrial carcinoma, DNA-ploidy is prognostic in hysterectomy and not in curettage samples. The ECPI is prognostically much stronger than the classic features widely used for therapy triage in pFIGO-1 and -2.

Supported by grant 28-1203 of the National Health Research Council of the Netherlands (ZonMw), a grant of the Comprehensive Cancer Center Amsterdam, and grant 97-98 of the Stichting Bevordering Diagnostische Morfometrie.

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