ABSTRACT
The PRAME (preferentially expressed antigen of melanoma) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared with malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the messenger RNA (mRNA) and protein levels. Quantitative real-time polymerase chain reaction analysis of 126 müllerian carcinomas and 23 malignant mesotheliomas showed significantly higher PRAME mRNA expression in the former tumor (P < .001; test sensitivity and specificity, 89% and 91%, respectively). PRAME protein was expressed in 41 of 50 müllerian carcinomas and 0 of 30 mesotheliomas using Western blotting (P < .001; test sensitivity and specificity, 82% and 100%, respectively). PRAME levels in müllerian carcinoma were unrelated to survival; however, PRAME protein expression was up-regulated in solid metastases compared with primary carcinoma and effusions (P < .001). Our data confirm that PRAME effectively differentiates müllerian carcinoma from malignant mesothelioma at the mRNA and protein levels, suggesting a role in the diagnostic workup of serosal cancers.
Subject(s)
Antigens, Neoplasm/genetics , Cystadenocarcinoma, Serous/diagnosis , Mesothelioma/diagnosis , Ovarian Neoplasms/diagnosis , Peritoneal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cystadenocarcinoma, Serous/genetics , Diagnosis, Differential , Female , Gene Expression , Humans , Mesothelioma/genetics , Mesothelioma/secondary , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/metabolism , RNA, Messenger/metabolismABSTRACT
The EHF (Ets homologous factor) gene 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 level in a larger series. We analyzed the diagnostic role of EHF in 98 ovarian serous carcinoma effusions, 23 malignant mesothelioma specimens (20 effusions, 3 surgical specimens), and 28 primary ovarian serous carcinomas using quantitative real-time polymerase chain reaction. Expression levels of EHF in ovarian carcinoma were additionally investigated for association with clinicopathologic parameters and survival. Quantitative real-time polymerase chain reaction analysis showed significantly higher expression of EHF mRNA in ovarian carcinoma effusions and in primary ovarian carcinoma compared to malignant mesothelioma effusions (P < .001 for both). EHF mRNA expression was additionally higher in primary ovarian carcinomas compared to effusions of this cancer (P < .001). In univariate analysis for all patients with effusions, higher EHF mRNA levels were associated with a trend for shorter progression-free survival (P = .066), which became significant in analysis of 45 patients with primary diagnosis pre-chemotherapy effusions (P = .01). In Cox multivariate analysis, EHF mRNA expression was an independent predictor of poor progression-free survival for all patients and patients with primary diagnosis pre-chemotherapy effusions (P = .033 and P = .009, respectively). EHF mRNA levels differentiate ovarian carcinoma from malignant mesothelioma and may thus be of diagnostic value in this setting. EHF may be a novel prognostic marker in ovarian carcinoma.
Subject(s)
Cystadenocarcinoma, Serous/mortality , Mesothelioma/mortality , Ovarian Neoplasms/mortality , Transcription Factors/genetics , Adult , Aged , Aged, 80 and over , Ascitic Fluid/pathology , Biomarkers, Tumor/genetics , Cohort Studies , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/therapy , Diagnosis, Differential , Disease-Free Survival , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Mesothelioma/genetics , Mesothelioma/pathology , Mesothelioma/therapy , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Pleural Effusion, Malignant/pathology , Prognosis , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Survival RateABSTRACT
Scavenger receptor class A, member 3 (SCARA3) was previously found to be overexpressed in ovarian/primary peritoneal carcinoma (OC/PPC) compared with breast carcinoma effusions by global gene expression analysis. The present study aimed to validate this finding applying quantitative PCR and analyzing the association between SCARA3 expression and clinicopathologic parameters in a large OC cohort. SCARA3 messenger RNA (mRNA) expression was analyzed in 127 effusions (103 ovarian/peritoneal/fallopian tube carcinomas, 9 breast carcinomas, 15 malignant mesotheliomas [MM]), and 30 solid primary OCs. The association between OC SCARA3 levels and clinicopathologic parameters was investigated. SCARA3 mRNA was expressed in all effusions, irrespective of tumor type. However, transcript levels were significantly higher in OC compared with breast carcinoma (P < .001) and MM (P = .011) effusions. Primary OCs and effusions had comparable expression levels. Higher SCARA3 expression was found in disease recurrence postchemotherapy compared with primary diagnosis prechemotherapy OC effusions (P = .001), and this difference was significant for treatment with both platinum agents (P = .006) and paclitaxel (P = .002). SCARA3 levels in effusions and primary carcinomas were unrelated to patient age, tumor grade, FIGO stage, residual tumor volume after surgery, response to chemotherapy, or survival (P > .05 for all). In conclusion, SCARA3 mRNA by quantitative PCR is highly expressed in OC and may aid in differentiating this tumor from other cancers, particularly breast carcinoma, in effusions. The consistently high SCARA3 levels in both primary carcinomas and metastatic cells in effusions, and its up-regulation along disease progression from diagnosis to recurrence, suggest a role in ovarian cancer biology.
