Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study
| Autor: | Shamshad Ali, Paul DiSilvestro, Russell J. Broaddus, Louise A. Brinton, Feng Gao, Shashikant Lele, Matthew A. Powell, David G. Mutch, Richard J. Zaino, David E. Cohn, Alexis Chassen, Paul J. Goodfellow, Caroline C. Billingsley, Heather A. Lankes, Colin C. Pritchard, Michael L. Pearl, Nilsa C. Ramirez, Amy P. Schmidt, Lisa M. Landrum, Luke V. Simmons, Floor J. Backes, Melissa A. Geller, Heather Hampel |
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| Rok vydání: | 2015 |
| Předmět: |
Oncology
Cancer Research DNA Mismatch Repair 0302 clinical medicine Early Detection of Cancer Mismatch Repair Endonuclease PMS2 Adenosine Triphosphatases Gynecologic Cancer 0303 health sciences Age Factors Nuclear Proteins Gync13 ORIGINAL REPORTS Middle Aged Immunohistochemistry Lynch syndrome Pedigree 3. Good health DNA-Binding Proteins Gene Expression Regulation Neoplastic MutS Homolog 2 Protein Population Surveillance 030220 oncology & carcinogenesis DNA methylation Female Microsatellite Instability DNA mismatch repair MutL Protein Homolog 1 Adult congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Gynecologic oncology MLH1 03 medical and health sciences Germline mutation Predictive Value of Tests Internal medicine medicine Humans Genetic Testing neoplasms Germ-Line Mutation Adaptor Proteins Signal Transducing Aged 030304 developmental biology business.industry Endometrial cancer nutritional and metabolic diseases Microsatellite instability DNA Methylation medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis digestive system diseases Endometrial Neoplasms DNA Repair Enzymes business |
| Zdroj: | Journal of Clinical Oncology |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS. Patients and Methods ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women. Results Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years. Conclusion Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age > 60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age < 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease. |
| Databáze: | OpenAIRE |
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