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Differences in Prognostic Molecular Markers between Women Over and Under 45 Years of Age with Advanced Ovarian Cancer

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, ² Division of Hematology/Oncology, Department of Medicine, ³ Department of Pathology, ⁴ Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center, Orange, California; ⁵ Department of Pathology, Long Beach Memorial Medical Center, Long Beach, California; and ⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California

Purpose: The purpose of this study was to determine whether differences in molecular markers might explain the better prognosis of women 45 years of age versus women >45 years of age diagnosed with ovarian cancers.

Experimental Design: Tissue sections from women with stage III–IV ovarian cancers were examined for expression of CD34, p53, and HER2. The Kaplan-Meier method and Cox Proportional Hazard analyses were used to identify predictors for outcome.

Results: Fifty-two women 45 years of age were matched with 52 women who were >45 years old. Of the 46 available tissue sections, 24 were from the younger age group (mean age, 41 years), and 22 were from the older age group (mean age, 61 years). Based on CD34 expression, tumors from women >45 years of age had lower microvessel density (MVD) compared with tumors of younger women (10.3 versus 16.1 microvessels per x400 field; P = 0.03). Lower MVD (11 microvessels per x400 field) predicted for a worse prognosis than higher MVD (>11 microvessels per x400 field) in the overall study group (P = 0.001) and within the older subgroup (P = 0.03). The expressions of p53 (P = 0.13) and HER2 (P = 0.49) did not vary between the two age groups. The median survivals of those with tumors that overexpressed p53 and HER2 were 28.6 and 23.9 months compared with 51.7 and 38.6 months in those with cancers that underexpressed these markers, respectively (P = 0.09 for p53, P = 0.15 for HER2).

Conclusions: Ovarian cancers in women >45 years of age had lower MVD compared with those in women 45 years of age. Lower MVD was an independent prognostic factor for decreased survival. Lower frequency of neovascularization in these cancers may contribute to the decreased survival observed in women >45 years of age.