Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch syndrome among US cancer programs and follow-up of abnormal results.

PURPOSE Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established tools to screen for Lynch syndrome (LS). Although many cancer centers have adopted these tools as reflex LS screening after a colorectal cancer diagnosis, the standard of care has not been established, and no formal studies have described this practice in the United States. The purpose of this study was to describe prevalent practices regarding IHC/MSI reflex testing for LS in the United States and the subsequent follow-up of abnormal results. MATERIALS AND METHODS A 12-item survey was developed after interdisciplinary expert input. A letter of invitation, survey, and online-survey option were sent to a contact at each cancer program. A modified Dillman strategy was used to maximize the response rate. The sample included 39 National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs), 50 randomly selected American College of Surgeons-accredited Community Hospital Comprehensive Cancer Programs (COMPs), and 50 Community Hospital Cancer Programs (CHCPs). RESULTS The overall response rate was 50%. Seventy-one percent of NCI-CCCs, 36% of COMPs, and 15% of CHCPs were conducting reflex IHC/MSI for LS; 48% of the programs used IHC, 14% of the programs used MSI, and 38% of the programs used both IHC and MSI. One program used a presurgical information packet, four programs offered an opt-out option, and none of the programs required written consent. CONCLUSION Although most NCI-CCCs use reflex IHC/MSI to screen for LS, this practice is not well-adopted by community hospitals. These findings may indicate an emerging standard of care and diffusion from NCI-CCC to community cancer programs. Our findings also described an important trend away from requiring written patient consent for screening.

[1]  J. Cubiella,et al.  5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. , 2011, Gastroenterology.

[2]  R. Sharp,et al.  Informed consent to microsatellite instability and immunohistochemistry screening for Lynch syndrome , 2011, Genetics in Medicine.

[3]  Michael S. Rentz,et al.  Immunohistochemical Staining for DNA Mismatch Repair Proteins in Intestinal Tract Carcinoma: How Reliable are Biopsy Samples? , 2011, The American journal of surgical pathology.

[4]  A. de la Chapelle,et al.  The Search for Unaffected Individuals with Lynch Syndrome: Do the Ends Justify the Means? , 2011, Cancer Prevention Research.

[5]  C. Boland,et al.  Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population , 2010, Cancer Prevention Research.

[6]  R. Labianca,et al.  Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Angela P. Wetzel Internet, mail, and mixed‐mode surveys: The tailored design method , 2010 .

[8]  T. Tuohy,et al.  Hereditary and familial colon cancer. , 2010, Gastroenterology.

[9]  H. Hampel Point: justification for Lynch syndrome screening among all patients with newly diagnosed colorectal cancer. , 2010, Journal of the National Comprehensive Cancer Network : JNCCN.

[10]  Cheri Manning,et al.  Facilitating informed decisions regarding microsatellite instability testing among high-risk individuals diagnosed with colorectal cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Richard D Kolodner,et al.  Comprehensive molecular analysis of mismatch repair gene defects in suspected Lynch syndrome (hereditary nonpolyposis colorectal cancer) cases. , 2009, Cancer research.

[12]  Yun Yen,et al.  NCCN clinical practice guidelines in oncology: hepatobiliary cancers. , 2009, Journal of the National Comprehensive Cancer Network : JNCCN.

[13]  M. Kruhøffer,et al.  Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression , 2009, BMC Cancer.

[14]  Heather Hampel,et al.  Feasibility of screening for Lynch syndrome among patients with colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  P. Maisonneuve,et al.  Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps. , 2008, Gastroenterology.

[16]  B. Levin,et al.  Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. , 2008, Gastroenterology.

[17]  W. Frankel,et al.  The frequency of Muir-Torre syndrome among Lynch syndrome families. , 2008, Journal of the National Cancer Institute.

[18]  J. Cucherousset,et al.  Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer. , 2007, Anticancer research.

[19]  L. Aaltonen,et al.  BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing , 2004, Journal of Medical Genetics.

[20]  D. Bowen,et al.  Colorectal Tumour Microsatellite Instability Test Results: Perspectives from Patients , 2004, Hereditary cancer in clinical practice.

[21]  Sudhir Srivastava,et al.  Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. , 2004, Journal of the National Cancer Institute.

[22]  H. Lynch Cancer family history and genetic testing: are malpractice adjudications waiting to happen? , 2002, American Journal of Gastroenterology.

[23]  J. P. Dunn Colorectal cancer screening. , 1997, The New Zealand medical journal.

[24]  D. Ward,et al.  Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancer , 1994, Nature.

[25]  N. Copeland,et al.  The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer , 1993, Cell.

[26]  E. Rogers,et al.  Diffusion of Innovations , 1964 .

[27]  Monica R McClain,et al.  EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome , 2009, Genetics in Medicine.

[28]  Jeffrey R. Botkin,et al.  Summary of Recommendations: The Evaluation of Genomic Applications , 2022 .

[29]  H. Lynch,et al.  Failure to diagnose hereditary colorectal cancer and its medicolegal implications , 1999, Diseases of the colon and rectum.