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Increased Cyclin D1 Expression Is Associated with Features of Malignancy and Disease Recurrence in Ovarian Tumors

Department of Preclinical Oncology, Section of Pharmacology and Neuroscience, Istituto Nazionale Ricerca Cancro [F. B., M. C., C. B., A. A.], and Department of Obstetrics and Gynecology [N. R., G. F., F. P.], University of Genoa, Largo Rosanna Benzi, 10-16132 Genoa, Italy

Alterations in the expression of cyclin D1 have been reported frequently in several human cancers, but their significance in the multistep model of carcinogenesis has been scantly described. To define the pattern of cyclin D1 expression in the development of ovarian cancer and clinical outcome, 55 cases of benign ovarian tumors, 12 borderline cases, and 37 ovarian carcinomas (32 primary and 5 recurrent carcinomas) were studied. Analyses were carried out on fresh tumor specimens by Western blotting and reverse transcription-PCR and provided significant superimposable results (P = 0.00001). Cyclin D1 abundance was classed according to the densitometric values as undetectable, detectable, well detectable, and highly detectable. A significant increase (P < 0.000001) in median cyclin D1 values was observed from benign (0.038; range, 0.001–0.705) to borderline (0.226; range, 0.001–0.623) to malignant (0.347; range, 0.027–2.330) to recurrent (0.887; range, 0.309–2.2260) tumors. In addition, higher median cyclin D1 values were reported in serous carcinomas (P = 0.058) and advanced-stage diseases (P = 0.003). Survival analyses carried out in the 32 primary carcinomas showed no significant difference in overall survival between detectable versus well/highly detectable cyclin D1 neoplasms. Conversely, a significant relationship between cyclin D1 expression and progression-free survival was found (P = 0.031). These results may elucidate the function of altered cyclin D1 expression in ovarian tumorigenesis and provide a basis for additional studies on its prognostic role.

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