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.


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).


CONCLUSIONS
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.
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland marek.cybulski.69@gmail.com marekc@bg.umlub.pl.
Marek
M
Cybulski
Department of Neurosurgery and Children's Neurosurgery, Medical University of Lublin, Lublin, Poland.
Bożena
B
Jarosz
Department of Gynecology and Oncologic Gynecology, Military Medical Institute, Warsaw, Poland.
Andrzej
A
Nowakowski
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Witold
W
Jeleniewicz
Third Department of Gynecologic Oncology, St. John's Cancer Center Lublin, Lublin, Poland.
Elżbieta
E
Kutarska
First Department of Oncologic Gynecology and Gynecology, Medical University of Lublin, Lublin, Poland.
Wiesława
W
Bednarek
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
Andrzej
A
Stepulak
D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D019925:Cyclin A / Q000032:analysis*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D051840:Y-Box-Binding Protein 1 / Q000032:analysis*
D019925:Cyclin A; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human
Cyclin A; YB-1; chemotherapy; ovarian cancer; progression