Systematic Review and Meta-analysis of Ovarian Cancers: Estimation of Microsatellite-High Frequency and Characterization of Mismatch Repair Deficient Tumor Histology

Purpose: A meta-analytic approach was used to estimate the frequency of: ( a ) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and ( b ) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers. Methods: A systematic search of the Medl...

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Bibliographic Details
Published in:Clinical cancer research 2008-11, Vol.14 (21), p.6847-6854
Main Authors: PAL, Tuya, PERMUTH-WEY, Jenny, KUMAR, Ambuj, SELLERS, Thomas A
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
DNA Mismatch Repair
Female
Female genital diseases
Gynecology. Andrology. Obstetrics
Humans
Medical sciences
meta-analysis
systematic review
Microsatellite Instability
mismatch repair deficiency
histologic subtypes
ovarian cancer
microsatellite instability
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Pharmacology. Drug treatments
Phenotype
Tumors
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Summary:Purpose: A meta-analytic approach was used to estimate the frequency of: ( a ) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and ( b ) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers. Methods: A systematic search of the Medline electronic database was conducted to identify articles published between January 1, 1966, and December 31, 2007, that examined MMR deficiency in ovarian cancers. Data were extracted on the study population, sample size, MSI-H frequency, and histology of MMR-deficient ovarian tumors. Results: The pooled proportion of MSI-H ovarian cancers was 0.12 [95% confidence interval (CI), 0.08-0.17] from 18 studies with 977 cases. The proportion of histologic subtypes in the pooled analysis from 15 studies with 159 cases was serous at 0.32 (95% CI, 0.20-0.44), mucinous at 0.19 (95% CI, 0.12-0.27), endometrioid at 0.29 (95% CI, 0.22-0.36), clear cell at 0.18 (95% CI, 0.09-0.28), and mixed at 0.24 (95% CI, 0.07-0.47). There was significant heterogeneity between studies. Conclusions: The frequency of the MSI-H phenotype in unselected ovarian cancers approximates 12%. MMR-deficient ovarian cancers also seem to be characterized by an overrepresentation of nonserous histologic subtypes. Knowledge of histologic subtype may aid clinicians in identifying the relatively large proportion of ovarian cancers due to MMR defects; such knowledge has potential implications for medical management.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-08-1387