RESUMO
The aim of the present study was to investigate the expression and clinical role of the aurora A and aurora B kinases in primary and metastatic serous ovarian carcinoma. AURKA and AURKB messenger RNA expression was investigated in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction. Aurora A and aurora B protein expression by immunohistochemistry was additionally analyzed in 147 tumors. Messenger RNA and protein expression at different anatomical sites were studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. AURKA and AURKB messenger RNA and their protein product were demonstrated in all primary carcinomas, solid metastases, and effusions. The expression of AURKA messenger RNA and aurora A protein was higher in effusions compared with solid specimens (P = .003 and P = .006, respectively). AURKB messenger RNA expression was higher in primary carcinomas, and solid metastases obtained prechemotherapy compared with postchemotherapy (P < .001 and P = .012, respectively), with no such difference in effusions (P > .05). Low aurora B protein expression was associated with primary chemotherapy resistance (P = .006) and poor treatment response (P = .013) in prechemotherapy effusions. No significant association was found between messenger RNA levels or protein expression and progression-free or overall survival. The present study documents for the first time frequent aurora A and aurora B expression in metastatic ovarian carcinoma, suggesting a role in cancer progression, with higher aurora A expression in effusions compared with primary carcinomas and solid metastases. Low AURKB messenger RNA expression in prechemotherapy effusions might be predictive of intrinsic chemotherapy resistance.
Assuntos
Cistadenocarcinoma Seroso/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Adulto , Idoso , Aurora Quinase A , Aurora Quinase B , Aurora Quinases , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Proteínas Inibidoras de Apoptose/biossíntese , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Metástase Neoplásica/fisiopatologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Proteínas Proto-Oncogênicas c-akt/biossíntese , RNA Mensageiro/metabolismo , Survivina , Tubulina (Proteína)/biossínteseRESUMO
Rab25, an epithelial-specific member of the Rab family of small GTPases, was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the mRNA and protein level. Quantitative PCR analysis of 112 Müllerian serous carcinomas (84 effusions, 28 primary ovarian carcinomas) and 22 malignant mesotheliomas (19 effusions, 3 solid specimens) showed significantly higher RAB25 mRNA expression in the former tumor (p < 0.001). Immunohistochemical analysis of Rab25 protein expression in 245 effusions showed significantly higher expression of this protein in Müllerian serous carcinoma compared to malignant mesothelioma (189/209 vs. 12/36 positive tumors, respectively; p < 0.001). Immunostaining of 101 patient-matched solid Müllerian carcinoma specimens (34 primary carcinomas, 67 metastases) showed expression levels comparable to effusions (94/101 positive specimens; p > 0.05). Rab25 mRNA and protein expression levels in Müllerian carcinoma effusions did not correlate with overall or progression-free survival. Our data confirm that Rab25 effectively differentiates Müllerian carcinomas from malignant mesothelioma at the mRNA and protein level, suggesting a role in the diagnostic work-up of serosal cancers.
