Abstract
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.
Copyright (c) 2006 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor / analysis*
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Biomarkers, Tumor / genetics
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CDC2-CDC28 Kinases
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Carrier Proteins / analysis
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Carrier Proteins / genetics
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Cdc20 Proteins
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Cell Cycle Proteins / analysis
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Cell Cycle Proteins / genetics
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Cellular Apoptosis Susceptibility Protein / analysis
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Cellular Apoptosis Susceptibility Protein / genetics
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Cyclin E / analysis
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Cyclin E / genetics
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Cyclin-Dependent Kinases / analysis
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Cyclin-Dependent Kinases / genetics
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Cystadenocarcinoma, Serous / genetics
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Cystadenocarcinoma, Serous / metabolism
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Cystadenocarcinoma, Serous / pathology*
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Female
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Gene Expression Profiling
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Glycodelin
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Glycoproteins / analysis
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Glycoproteins / genetics
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Humans
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Immunohistochemistry
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MAP Kinase Kinase 1 / analysis
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MAP Kinase Kinase 1 / genetics
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Middle Aged
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Neoplasm Staging
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Oligonucleotide Array Sequence Analysis
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Oncogene Proteins / analysis
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Oncogene Proteins / genetics
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology*
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Pregnancy Proteins / analysis
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Pregnancy Proteins / genetics
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Prognosis
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-met
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Receptors, Aryl Hydrocarbon / analysis
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Growth Factor / analysis
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Receptors, Growth Factor / genetics
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Smad3 Protein / analysis
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Smad3 Protein / genetics
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Survival Analysis
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Tissue Array Analysis / methods*
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ran GTP-Binding Protein / analysis
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ran GTP-Binding Protein / genetics
Substances
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AHR protein, human
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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CCNE1 protein, human
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CKS1B protein, human
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Carrier Proteins
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Cdc20 Proteins
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Cell Cycle Proteins
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Cellular Apoptosis Susceptibility Protein
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Cyclin E
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Glycodelin
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Glycoproteins
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Oncogene Proteins
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PAEP protein, human
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Pregnancy Proteins
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Proto-Oncogene Proteins
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RAN protein, human
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Receptors, Aryl Hydrocarbon
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Receptors, Growth Factor
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SMAD3 protein, human
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Smad3 Protein
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CDC20 protein, human
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MET protein, human
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Proto-Oncogene Proteins c-met
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CDC2-CDC28 Kinases
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Cyclin-Dependent Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human
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ran GTP-Binding Protein