Abstract
BackgroundCyclin A1 is essential for male gametopoiesis. In acute myeloid leukemia, it acts as a leukemia-associated antigen. Cyclin A1 expression has been reported in several epithelial malignancies, including testicular, endometrial, and epithelial ovarian cancer (EOC). We analyzed Cyclin A1 expression in EOC and its correlation with clinical features to evaluate Cyclin A1 as a T-cell target in EOC.MethodsCyclin A1 mRNA expression in EOC and healthy tissues was quantified by microarray analysis and quantitative real-time PCR (qRT-PCR). Protein expression in clinical samples was assessed by immunohistochemistry (IHC) and was correlated to clinical features.ResultsCyclin A1 protein was homogeneously expressed in 43 of 62 grade 3 tumor samples and in 1 of 10 grade 2 specimens (p < 0.001). Survival analysis showed longer time to progression (TTP) among patients with at least moderate Cyclin A1 expression (univariate: p = 0.018, multivariate: p = 0.035). FIGO stage, grading, age, macroscopic residual tumor after debulking, and peritoneal carcinomatosis / distant metastasis had no impact on TTP or overall survival (OS).ConclusionCyclin A1 is highly expressed in most EOCs. The mechanism behind the prolonged TTP in patients with high Cyclin A1 expression warrants further investigation. The frequent, selectively high expression of Cyclin A1 in EOC makes it a promising target for T-cell therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1824-6) contains supplementary material, which is available to authorized users.
Highlights
Cyclin A1 is essential for male gametopoiesis
Patients Cyclin A1 expression was analyzed immunohistochemically in tumor material from 72 patients primarily with advanced epithelial ovarian cancer (EOC) who underwent cytoreductive surgery followed by platinum-based chemotherapy
Cyclin A1 is homogenously expressed in most high-grade epithelial ovarian cancers To identify tumor entities with frequent aberrant Cyclin A1 expression, a microarray panel from the NCBI
Summary
Cyclin A1 is essential for male gametopoiesis. In acute myeloid leukemia, it acts as a leukemia-associated antigen. Cyclin A1 expression has been reported in several epithelial malignancies, including testicular, endometrial, and epithelial ovarian cancer (EOC). EOCs are immunogenic tumors with spontaneous T-cell responses in more than 50 % of patients [5,6,7]. While the presence of tumor-infiltrating intraepithelial lymphocytes is associated with prolonged progression-free survival (PFS) and overall survival (OS), immune evasive factors, such as the expansion of regulatory T-cells or the expression of PD-L1 and endothelin B receptor, correlate with poor survival [8, 9]. Patients with advanced stage EOC after initial debulking and cytostatic treatment are excellent candidates for targeted T-cell therapy because of their minimal tumor burden and tumor immunogenicity, which may be enhanced by previous paclitaxel treatment [5,6,7]
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