Cyclin A correlates with YB1, progression and resistance to chemotherapy in human epithelial ovarian cancer

Background: Cyclin A is a cell-cycle regulatory gene and its overexpression promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a transcription/translation factor involved in tumor growth, invasion, and drug resistance. We investigated whether an association exists between protein products of these genes in epithelial ovarian cancer (EOC) specimens and clinicopathological parameters, patient response and EOC sensitivity to platinum-based first-line chemotherapy.

Patients and methods: Cyclin A and YB1 expression were analyzed by immunohistochemistry in 54 human primary EOC tissues. Immunolabeling of both proteins was graded according to their staining intensity (scale 0-3) and the proportion of immunostained cancer cells (scale 0-4) to obtain a staining index (SI; value=0-12).

Results: Significantly higher cyclin A immunostaining (SI≥4) in EOC specimens was discovered in patients with advanced (International Federation of Gynaecology and Obstetrics (FIGO) III and IV, p=0.003), poorly differentiated (G3, p<0.001) tumors, and tumors of those with residual disease>1 cm (p=0.001). YB1 immunostaining was significantly higher in EOCs from patients with suboptimal debulking (p=0.025). Over-expression of cyclin A (SI≥9) in EOCs was significantly linked with poorer patient response (p=0.001) and higher resistance of tumors to platinum-based first-line chemotherapy (p=0.007), while immunolabeling of YB1 in EOCs was not significantly associated with either of these variables (p>0.05). Cyclin A expression was significantly and positively correlated with that of YB1 (R=0.588, p<0.001).

Conclusion: Increased cyclin A expression in EOC is related to a more aggressive tumor behavior and predicts the response of patients to first-line platinum-based chemotherapy.