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.
Ouellet
Véronique
V
Centre de Recherche du Centre Hospitalier de l'Université de Montréal/Institut du cancer de Montréal, Montreal, Canada.
Provencher
Diane M
DM
Maugard
Christine M
CM
Le Page
Cécile
C
Ren
Fengge
F
Lussier
Christian
C
Novak
Jaroslav
J
Ge
Bing
B
Hudson
Thomas J
TJ
Tonin
Patricia N
PN
Mes-Masson
Anne-Marie
AM
D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014407:Tumor Cells, Cultured
D005819:Genetic Markers