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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.
J Clin Oncol 2015; 33(36):4301-8JC

Abstract

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.

Authors+Show Affiliations

Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA. paul.goodfellow@osumc.edu.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.Paul J. Goodfellow, Caroline C. Billingsley, David E. Cohn, Heather Hampel, Alexis S. Chassen, Luke V. Simmons, and Floor Backes, Ohio State University; Nilsa Ramirez, Research Institute at Nationwide Children's Hospital, Columbus, OH; Heather A. Lankes and Shamshad Ali, NRG Oncology Statistics and Data Management Center; Shashikant B. Lele, Roswell Park Cancer Institute, Buffalo; Michael L. Pearl, Stony Brook University Hospital, Stony Brook, NY; Russell J. Broaddus, University of Texas MD Anderson Cancer Center, Houston, TX; Colin C. Pritchard, University of Washington, Seattle, WA; Amy P. Schmidt, Feng Gao, Matthew A. Powell, and David Mutch, Washington University School of Medicine, St Louis, MO; Louise A. Brinton, National Cancer Institute, Washington, DC; Lisa M. Landrum, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Melissa A. Geller, University of Minnesota, Minneapolis, MN; Paul A. DiSilvestro, Women and Infants Hospital of Rhode Island, Providence, RI; and Richard J. Zaino, Penn State Milton S. Hershey Medical Center, Hershey, PA.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26552419

Citation

Goodfellow, Paul J., et al. "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." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 33, no. 36, 2015, pp. 4301-8.
Goodfellow PJ, Billingsley CC, Lankes HA, et al. 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. J Clin Oncol. 2015;33(36):4301-8.
Goodfellow, P. J., Billingsley, C. C., Lankes, H. A., Ali, S., Cohn, D. E., Broaddus, R. J., ... Mutch, D. (2015). 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. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 33(36), pp. 4301-8. doi:10.1200/JCO.2015.63.9518.
Goodfellow PJ, et al. 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. J Clin Oncol. 2015 Dec 20;33(36):4301-8. PubMed PMID: 26552419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Goodfellow,Paul J, AU - Billingsley,Caroline C, AU - Lankes,Heather A, AU - Ali,Shamshad, AU - Cohn,David E, AU - Broaddus,Russell J, AU - Ramirez,Nilsa, AU - Pritchard,Colin C, AU - Hampel,Heather, AU - Chassen,Alexis S, AU - Simmons,Luke V, AU - Schmidt,Amy P, AU - Gao,Feng, AU - Brinton,Louise A, AU - Backes,Floor, AU - Landrum,Lisa M, AU - Geller,Melissa A, AU - DiSilvestro,Paul A, AU - Pearl,Michael L, AU - Lele,Shashikant B, AU - Powell,Matthew A, AU - Zaino,Richard J, AU - Mutch,David, Y1 - 2015/11/09/ PY - 2015/11/11/entrez PY - 2015/11/11/pubmed PY - 2016/4/29/medline SP - 4301 EP - 8 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 33 IS - 36 N2 - 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. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/26552419/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_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2015.63.9518?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -