Robin F Irons1, Krysta M Contino2, Janice J Horte3, Brooke Levin4, Kristin D Mattie4, Margaret Wight5, Michael E Kwiatt6, Kathryn C Behling7,8, Tina B Edmonston8, Steven J McClane9. 1. Department of Surgery, Cooper University Hospital, Office of Surgical Education, 3 Cooper Plaza, Suite 411, Camden, NJ, 08103, USA. irons-robin@cooperhealth.edu. 2. Department of Medicine, Cooper University Hospital, 401 Haddon Avenue, E&R Building, Third Floor, Camden, NJ, 08103, USA. 3. Medical Genetics, Stollery Children's Hospital, 8-53 MSB, 8440-112 St, Edmonton, AB, T6G 2H7, Canada. 4. MD Anderson Cancer Center at Cooper, Cooper University Hospital, 2 Cooper Plaza, 400 Haddon Avenue, Camden, NJ, 08103, USA. 5. Tumor Registry at Kennedy Cancer Center, 900 Medical Center Drive, Suite 211,, Sewell, NJ, 08080, USA. 6. Department of Colorectal Surgery, Cooper University Hospital, 2 Cooper Plaza, Camden, NJ, 08103, USA. 7. Department of Biomedical Sciences, Cooper Medical School of Rowan University, 1 Cooper Plaza, Camden, NJ, 08103, USA. 8. Department of Pathology, Cooper University Hospital, 1 Cooper Plaza, Camden, NJ, 08103, USA. 9. Department of Colorectal Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 403, Camden, NJ, 08103, USA.
Abstract
PURPOSE: Lynch syndrome (LS) is a hereditary condition that increases one's risk of developing colorectal, endometrial, and other extracolonic cancers. MD Anderson Cancer Center at Cooper implemented a reflex screening protocol for DNA mismatch repair (dMMR) deficiency. Those with findings suspicious for LS were referred for genetic counseling (GC). Our goal was to assess compliance with GC and factors associated with successful follow-up. METHODS: Immunohistochemistry (IHC) for the MMR proteins MSH2, MLH1, MSH6, and PMS2 was performed on all colorectal tumor resections from patients ≤70 years old and all stage II cancers. Tumors with loss of MLH1/PMS2 were subsequently tested for BRAF mutation or MLH1 promoter methylation to identify tumors with likely epigenetic inactivation of MLH1. Patients with loss of MLH1/PMS2 without BRAF mutations or with absence of MLH1 promoter methylation and those with loss of MSH2/MSH6 were referred to GC. Compliance with GC was assessed. RESULTS: Between March 2014 and August 2016, 203 tumors were tested by IHC. Fifteen (7.4%) patients had abnormal MMR protein expression patterns in the absence of BRAF mutation or MLH1 promoter methylation suggestive of possible LS. GC compliance was 35.7% overall and 85.7% in those with family history of LS-associated cancers. CONCLUSIONS: Overall, GC compliance was relatively low in our study. Interestingly, patients with a strong family history of LS-associated neoplasms were more likely to pursue GC. In the future, assessing and addressing barriers to seeking GC will provide opportunities to improve patient care through increased identification of patients with cancer predisposition syndromes.
PURPOSE:Lynch syndrome (LS) is a hereditary condition that increases one's risk of developing colorectal, endometrial, and other extracolonic cancers. MD Anderson Cancer Center at Cooper implemented a reflex screening protocol for DNA mismatch repair (dMMR) deficiency. Those with findings suspicious for LS were referred for genetic counseling (GC). Our goal was to assess compliance with GC and factors associated with successful follow-up. METHODS: Immunohistochemistry (IHC) for the MMR proteins MSH2, MLH1, MSH6, and PMS2 was performed on all colorectal tumor resections from patients ≤70 years old and all stage II cancers. Tumors with loss of MLH1/PMS2 were subsequently tested for BRAF mutation or MLH1 promoter methylation to identify tumors with likely epigenetic inactivation of MLH1. Patients with loss of MLH1/PMS2 without BRAF mutations or with absence of MLH1 promoter methylation and those with loss of MSH2/MSH6 were referred to GC. Compliance with GC was assessed. RESULTS: Between March 2014 and August 2016, 203 tumors were tested by IHC. Fifteen (7.4%) patients had abnormal MMR protein expression patterns in the absence of BRAF mutation or MLH1 promoter methylation suggestive of possible LS. GC compliance was 35.7% overall and 85.7% in those with family history of LS-associated cancers. CONCLUSIONS: Overall, GC compliance was relatively low in our study. Interestingly, patients with a strong family history of LS-associated neoplasms were more likely to pursue GC. In the future, assessing and addressing barriers to seeking GC will provide opportunities to improve patient care through increased identification of patients with cancer predisposition syndromes.
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