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Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. The histopathologic classification of endometrial lesions is a difficult task requiring extensive experience. The Gynecologic Oncology Group (GOG) conducted a study (GOG 167A) that was designed to estimate the frequency of endometrial cancer in hysterectomy specimens in subjects who had a biopsy diagnosis of atypical endometrial hyperplasia. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40 % of nuclei of the preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. While karyometric assessment does not provide a distinctive diagnostic criterion for an individual patient, it does provide a measure of risk for the development of invasive disease. Studies to support the diagnostic assessment of endometrial lesions by computer aided morphometric analyses go back over 30 years. These efforts were aimed at two objectives, the diagnostic distinction between benign and cancer, and procedures that allow a stratification of patients into risk groups for the development of myometrial invasion. The percentage of nuclei of preneoplastic phenotype in AEH lesions might serve as criterion for assessment of risk for the development of invasive disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4614. doi:1538-7445.AM2012-4614

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