Biomedical subjects

Véronique Ouellet

Publications and source records attributed to Véronique Ouellet.

5 recordsLinked to original sources

PubMed2006

SET complex in serous epithelial ovarian cancer.

With low cure rates but increasing diverse treatment options that provide variable remission times, ovarian cancer is increasingly being recognized as a chronic disease. This reality indicates the need for a better understanding of factors influencing disease progression. In a previous global analysis of gene expression, we identified genes differentially expressed when comparing serous epithelial ovarian tumors of low and high malignant potential (grade 0 vs grade 3). In this analysis, 4 out of 5 members of the SET complex, SET, APE1, NM23 and HMGB2, were highly expressed in invasive grade 3 tumors. To further investigate the expression of these genes and the fifth member of the SET complex (pp32), we performed immunohistochemistry, on a tissue array composed of 235 serous tumors of different grades and disease stages. A significant correlation between expression of all SET complex proteins and the tumor differentiation was observed (p < 0.05). When combining all tumors, overexpression of Nm23 (p = 0.04), Set (p = 0.004) and Ape1 (p = 0.004) was associated with the clinical stage of the disease. No marker by itself was associated with prognosis. The combination of a high level of Nm23 in the context of a low level of Set compared to all other combinations of these markers did confer a better prognosis (p = 0.03). When combined, high expression of Hmgb2 and low expression of Ape1 was also associated with patient prognosis (p = 0.05). These findings suggest that a strategy that sums the activities of different partners within a pathway may be more appropriate in designing nomograms for patient stratification.

Adult↗

PubMed2006

Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer.

Molecular profiling is a powerful approach to identify potential clinical markers for diagnosis and prognosis as well as providing a better understanding of the biology of epithelial ovarian cancer. On the basis of the analysis of HuFL expression data, we have previously identified genes that distinguish low malignant potential and invasive serous epithelial ovarian tumors. In this study, we used immunohistochemistry to monitor a subset of differently expressed candidates (Ahr, Paep, Madh3, Ran, Met, Mek1, Ccne1, Ccd20, Cks1 and Cas). A tissue array composed of 244 serous tumors of different grades (0-3) and stages (I-IV) was used in this analysis. All markers assayed presented differential protein expression between serous tumors of low and high grade. Significant differences in Ccne1 and Ran expression were observed in a comparison of low malignant potential and grade 1 tumor samples (p<0.01). In addition, irrespective of the grade, Ccne1, Ran, Cdc20 and Cks1 showed significant differences of expression in association with the clinical stage of disease. While high level of Ccne1 have previously been associated with poor outcomes, here we found that high level of either Ran or Cdc20 appear to be more tightly associated with a poor prognosis (p<0.001, 0.03, respectively). The application of these biomarkers in both the initial diagnosis and prognostic attributes of patients with epithelial ovarian tumors should prove to be useful in patient management.

Basic Helix-Loop-Helix Proteins↗

PubMed2006

From gene profiling to diagnostic markers: IL-18 and FGF-2 complement CA125 as serum-based markers in epithelial ovarian cancer.

We used an oligonucleotide-based DNA microarray to identify potential markers in 39 primary cultures of ovarian cancer specimens compared with 11 primary cultures of normal ovarian epithelia. Differential gene expression of IL-18 and FGF-2 was validated on a subset of samples by quantitative PCR and by IHC, using an independent tissue array of 90 cores of 20 normal ovarian surface epithelia and 70 EOCs representing different grades and pathologies of ovarian disease. We further compared, by ELISA, these two markers with CA125 in sera from 25 cancer-free and 47 ovarian cancer patients. IL-18 and FGF-2 proteins were significantly elevated in tumor tissues (p<0.04) and sera (p<0.05) from patients with ovarian cancer. In combination, the three markers (IL-18, FGF-2, and CA125) showed similar sensitivity in scoring for ovarian cancer (35/45 patients) compared to that of CA125 alone (37/45) and significantly improved the specificity of detection (20/25 patients) compared to each marker individually (15/25 for CA125; 18/25 FGF-2; 16/25 for IL-18). In conclusion we show that a combination of the three serum markers (IL-18, FGF-2 and CA125) is associated with EOC, with higher specificity than CA125 alone. Prospective studies with a large cohort of susceptible ovarian cancer patients will be required to expand these findings.

Biomarkers, Tumor↗

PubMed2005

Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling.

Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses were performed either in a primary culture or a tumor tissue model system and selected candidate genes showing a distinctive expression profile between LMPs and TOVs were identified using a class prediction approach based on three statistical methods of analysis. Both model systems appear relevant as candidate genes identified by either model allowed the proper reclassification of samples as either LMPs or TOVs. Selected candidate genes (CAS, CCNE1, LGALS8, ITGbeta3, ATP1B1, FLIP, KRT7 and KRT19) were validated by real-time quantitative PCR analysis and show differential expression between LMPs and TOVs. Immunohistochemistry analyses showed that the two tumor classes were distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These results define signature patterns for gene expression of LMPs and TOVs and identify gene candidates that warrant further study to deepen our understanding of the biology of EOC.

Diagnosis, Differential↗

PubMed2004

Signature of a silent killer: expression profiling in epithelial ovarian cancer.

With the sequencing of the human genome and the simultaneous development of high-throughput strategies, cancer biologists have entered an exciting new area for gene expression analysis, with the ability to glimpse higher order patterns of genetic and epigenetic alterations in complex diseases. Ovarian cancer biologists are rising to the challenge of applying these new technologies to this silent killer, with the eventual goal of improving the quality of life and long-term survival of patients. This review provides a summary of the disease, a description of available technologies and their application to the ovarian cancer problem, as well as a discussion on the challenges and opportunities related to DNA microarray expression profiling-based research, including downstream clinical applications.

Biomarkers, Tumor↗