Implementation/Feasibility of Universal Screening
A. Beamer LC, Grant JL, Espenschied CR, et al. Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch Syndrome among US cancer programs and follow-up of abnormal results. J Clin Oncol. 2012;30:1058-1063. [Abstract]
This study is the first to describe the prevalence of routine IHC/MSI colorectal tumor testing practices among U.S. cancer programs. A survey was sent to 39 NCI-designated comprehensive cancer centers (CCCs) and 100 randomly selected community hospital cancer programs. The overall response rate was 50%. Seventy-one percent of NCI-CCCs were performing IHC/MSI versus between 15-36% of programs in the community. Potential barriers to implementation of routine testing include the need for information and education for programs that are contemplating testing, and the importance of understanding issues with patient participation and follow-up. None of the programs currently performing reflex IHC/MSI required a separate informed consent. Routine testing of IHC/MSI on colorectal tumors is an emerging standard of care with the NCI-CCCs leading the field.
B. Canard G, Lefevre JH, Colas C, et al. Screening for Lynch syndrome in colorectal cancer: Are we doing enough? Ann Surg Oncol. 2012;19:809-816. [Abstract]
The authors screened 1040 consecutive colorectal cancer cases for IHC (MLH1, MSH2, MSH6) and MSI. After those with promoter methylation were identified, 62 (6%) patients had an abnormal result. 38 had germ-line testing in which a mutation was identified in 25 (65.8%). Bethesda criteria were not met in 23 of the 62 (37%) patients with an abnormal result. The authors recommend screening for LS in all patients with CRC, as 37% of possible Lynch cases would be missed by use of the Bethesda criteria alone. The authors recommend using both IHC and MSI as there can be a discordant result rate of up to 10%. Additionally, the uptake of germline genetic testing was lower in elderly patients and those without a family history of CRC, so these patients should be better educated about the benefits of genetic testing.
C. Bellcross CA, Bedrosian SR, Daniels E, et al. Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting. Genet Med. 2012;14:152-162. [Abstract]
Given the 2009 EGAPP recommendations to offer universal Lynch syndrome screening, the Office of Public Health Genomics at the Centers for Disease Control and Prevention convened a multidisciplinary meeting of clinical and public health experts to discuss possible approaches to meet this goal. They concluded that successful implementation of universal screening may be accomplished by developing a broadly coordinated public health approach with input from key stakeholders. The group also highlighted several challenges associated with universal testing including access, cost, provider knowledge and patient compliance with screening. Pilot implementation projects are needed to demonstrate effectiveness and provide additional evidence of the feasibility and utility of universal LS screening.
D. Schofield L, Grieu F, Goldblatt J, et al. A state-wide population-based program for detection of lynch syndrome based upon immunohistochemical and molecular testing of colorectal tumours. Fam Cancer. 2012;11:1-6. [Abstract]
In 2008, Western Australia implemented state-wide routine MSI and/or IHC testing on tumors from all patients diagnosed with CRC under <60 years of age as a first screen to identify individuals with Lynch syndrome. IHC was performed by 5 major pathology labs and tumors showing loss of MMR expression were sent to a single laboratory for MSI testing and BRAF analysis. Over a 2 year period, 270 cases were referred for MSI testing and 45 were eligible for germline testing. Results of germline testing indicated that the majority of LS cases were being identified in this region of Australia using routine, prospective MSI/IHC screening.