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  • Title: Prognostic markers for coexistent carcinoma in high-risk endometrial hyperplasia with negative D-score: significance of morphometry, hormone receptors and apoptosis for outcome prediction.
    Author: Ørbo A, Kaino T, Arnes M, Larsen K, Pettersen I, Moe B.
    Journal: Acta Obstet Gynecol Scand; 2009; 88(11):1234-42. PubMed ID: 19900140.
    Abstract:
    OBJECTIVES: Hysterectomy represents the current routine therapy for high-risk endometrial precancers. More sophisticated methods are needed for treatment decision among women who want to preserve fertility and seriously ill patients. Among women diagnosed with high-risk hyperplasia, approximately 40% show signs of endometrial cancer in the hysterectomy specimen. Thus, more sophisticated methods are needed to select the women at risk. SETTING: University Hospital of Tromsø, Regional Center for Gynecological Oncology in northern Norway. POPULATION: From 1999 to 2004, 258 consecutive patients had endometrial hyperplasia diagnosed by D-score; 57 among these were high-risk cases (D-score < 0) and 10 had coexisting endometrial carcinoma. No further cancers were detected after long-term follow-up (4-10 years). DESIGN: From the initial histological specimens, material from the 10 patients with cancer and from the 13 cases without cancer (high-risk D-score < 0) was analyzed with selected histomorphometric (architectural and nuclear) and immunohistochemical (hormone receptors and apoptotic) features blinded to the investigator. METHOD: Original slides were used for computerized histomorphometry (4-class rule and related procedures). Serial sections from the paraffin embedded material were used for immunohistochemical investigations. Immunohistochemical expression in glands and stroma was evaluated by the semi-quantitative H-score (ER-alpha, ER-beta, PR-A, PR-B, RCAS-1, Bcl-2, BAX, and Caspase-3). RESULTS: The histomorphometric 4-class rule differentiates between presence and absence of cancers with a sensitivity of 80% and specificity of 77%. Several morphometric and immunohistochemical features were significantly different in cases with cancer and hyperplasia. CONCLUSIONS: Histomorphometry seems superior in predicting coexistent carcinoma in high-risk endometrial hyperplasia and should be considered for clinical use.
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