Cancer-testis antigen cyclin A1 is broadly expressed in ovarian cancer and is associated with prolonged time to tumor progression after platinum-based therapy.
BACKGROUND
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). We analyzed Cyclin A1 expression in EOC and its correlation with clinical features to evaluate Cyclin A1 as a T-cell target in EOC.


METHODS
Cyclin 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.


RESULTS
Cyclin 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).


CONCLUSIONS
Cyclin 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.
Department of Pathology, Institute of Pathology, Charité - University Hospital Berlin, 10117, Berlin, Germany. ruza.arsenic@charite.de.
Ruza
R
Arsenic
Departement of Gynecology, University Hospital Berlin, 13353, Berlin, Germany. elena.braicu@charite.de.
Elena Ilona
EI
Braicu
Department of Hematology, Oncology and Tumor Immunology - University Hospital Berlin, 12200, Berlin, Germany. anne.letsch@charite.de.
Anne
A
Letsch
Department of Pathology, Institute of Pathology, Charité - University Hospital Berlin, 10117, Berlin, Germany. manfred.dietel@charite.de.
Manfred
M
Dietel
Departement of Gynecology, University Hospital Berlin, 13353, Berlin, Germany. jalid.sehouli@charite.de.
Jalid
J
Sehouli
Charité Cancer Comprehensive Center, Charité, 10117, Berlin, Germany. ulrich.keilholz@charite.de.
Ulrich
U
Keilholz
Department of Hematology, Oncology and Tumor Immunology - University Hospital Berlin, 12200, Berlin, Germany. sebastian.ochsenreither@charite.de.
Sebastian
S
Ochsenreither
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016190:Carboplatin / Q000627:therapeutic use; D056750:Cyclin A1 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D056750:Cyclin A1; D012333:RNA, Messenger; D016190:Carboplatin; D017239:Paclitaxel