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  • Original Paper
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Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling

Oncogene volume 24, pages 4672–4687 (2005)Cite this article

Abstract

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, ITGβ3, 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.

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Acknowledgements

We are grateful to Louise Champoux, Manon de Ladurantaye, Lise Portelance, Stéphanie Girard, Daniel Vincent and Kristina Martinu for technical assistance. We appreciate the assistance of Marie-Hélène Dufresne and Marie-Claude Guyot for immunohistochemistry, and Mario Filion for linear amplifications of RNA. We thank Dr A Alobaid for thoughtful comments. This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to A-MM-M, PNT, DMP and TJH. We recognize also the Fondation Jocelyn Gauvin for initial assistance in this research. Tumor banking was supported by the Banque de tissus et de données of the Réseau de recherche sur le cancer of the Fonds de la recherche en santé du Québec (FRSQ). VO was supported by studentships from the CIHR and Canderel fund of the Institut du cancer de Montréal. FR was supported by a Wyeth-CIHR sponsored fellowship and CMM by a fellowship from the Fondation pour la Recherche Médicale and a Bourse d'excellence from the Ministère de l'Education du Québec. PNT is a recipient of a Frazer, Monat and Mc Pherson Scholarship and the Stewart Fellowship in Research/Clinical Hematology and Oncology. TJH is recipient of an Investigator Award from CIHR and a Clinician–scientist Award in Translational Research from the Burroughs Wellcome Fund. DMP is a recipient of a Chercheur-Clinicien Senior, and A-MM-M is a recipient of a Chercheur National, all fellowships provided by the FRSQ.

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  1. Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM)/Institut du cancer de Montréal, Montreal, Canada

    Véronique Ouellet, Diane M Provencher, Christine M Maugard, Cécile Le Page, Fengge Ren & Anne-Marie Mes-Masson

  2. Division of Gynecologic Oncology, Université de Montréal, Montreal, Canada

    Diane M Provencher

  3. Department of Medicine, Université de Montréal, Montreal, Canada

    Christine M Maugard & Anne-Marie Mes-Masson

  4. Department of pathology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Canada

    Christian Lussier

  5. McGill University and Genome Quebec Innovation Centre, Montreal, Canada

    Jaroslav Novak, Bing Ge & Thomas J Hudson

  6. Department of Human Genetics, McGill University, Montreal, Canada

    Thomas J Hudson & Patricia N Tonin

  7. The Research Institute of McGill University Health Centre, Montreal, Canada

    Thomas J Hudson & Patricia N Tonin

  8. Department of Medicine, McGill University, Montreal, Canada

    Patricia N Tonin

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  1. Véronique Ouellet
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Ouellet, V., Provencher, D., Maugard, C. et al. Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling. Oncogene 24, 4672–4687 (2005). https://doi.org/10.1038/sj.onc.1208214

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