Molecular and Clinicopathological Analysis of Ovarian Carcinomas With and Without Microsatellite Instability

Background: Microsatellite instability (MSI) occurs in sporadic ovarian carcinomas. This study tests the hypothesis that ovarian carcinomas arising through the mutator pathway have distinctive clinical and molecular features that affect clinical outcome. Materials and Methods: The MSI status was eva...

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Bibliographic Details
Published in:Anticancer research 2004-01, Vol.24 (1), p.361-369
Main Authors: DELLAS, Athanassios, PUHL, Alex, SCHRAML, Peter, THOMKE, Sabine E, RÜSCHOFF, Josef, MIHATSCH, Michael J, MOCH, Holger
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Base Pair Mismatch
Biological and medical sciences
Carrier Proteins
DNA Repair
DNA, Neoplasm - genetics
DNA-Binding Proteins - biosynthesis
Female
Gene Dosage
Genomic Instability
Humans
Medical sciences
Microsatellite Repeats - genetics
MutL Protein Homolog 1
MutS Homolog 2 Protein
Neoplasm Proteins - biosynthesis
Neoplasm Staging
Nuclear Proteins
Nucleic Acid Hybridization
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Proto-Oncogene Proteins - biosynthesis
Survival Rate
Tumors
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Summary:Background: Microsatellite instability (MSI) occurs in sporadic ovarian carcinomas. This study tests the hypothesis that ovarian carcinomas arising through the mutator pathway have distinctive clinical and molecular features that affect clinical outcome. Materials and Methods: The MSI status was evaluated in 66 ovarian carcinomas and 11 epithelial ovarian tumors of low malignant potential. For the analysis with the microsatellite markers, a fluorescence-based PCR method was employed and the prognostic significance of the MSI status was assessed. DNA copy number changes in tumors with and without MSI were analyzed by comparative genomic hybridization. Results: High-frequency MSI (MSI-H) was found in 30% of the carcinomas, whereas low-frequency MSI (MSI-L) occurred in 32%. In LMP tumors, only MSI-L was detected (18%). There was a trend for tumors with MSI-H and MSI-L to have a poor prognosis, but this relationship did not reach significance (p=0.09 and p=0.07, respectively). MSI-H in carcinomas was significantly associated with poor differentiation (p=0.03) and higher clinical stage (p=0.03). No correlation was found between different histological types of ovarian carcinoma and the microsatellite status. In a multivariate analysis, MSI at the dinucleotide repeat D5S346 was found to be of independent prognostic significance (p
ISSN:0250-7005
1791-7530