[716] Revised Bethesda Guidelines Directing MSI Testing of Colorectal Cancers in Routine Surgical Pathology Practice: A Single Institution Experience

JC Post, M Bronner, B Leach, E Downs-Kelly, X Liu. Cleveland Clinic, Cleveland, OH

Background: Lynch syndrome (LS) is the most common hereditary form of colorectal cancer (CRC) with a known genetic basis. The revised 2004 Bethesda guidelines were developed to identify potential LS patients by guiding reflex testing of CRCs for microsatellite instability (MSI). This study was undertaken to retrospectively evaluate guideline use in routine surgical pathology practice, hypothesizing that a significant number of potential LS patients who are ≥60 years would be missed by guideline recommendations, when no additional clinical data are available to the pathologists.
Design: All CRC cases surgically resected from 11/06 to 3/09 were retrieved from the pathology database and analyzed for MSI testing rates in the following patient groups: group A: ≥60 yrs (n=286); group B: <50 yrs (n=62); and group C: 50-59 yrs (n=97). MSI testing was performed using a panel of 5 quasi-monomorphic mononucleotide repeat markers comparing cancers to matched normal control tissue with MSI-H defined as 2 markers showing instability. Reflex MSI testing was performed for MSI-H phenotype CRC morphology (groups A & C), or age <50 (group B).
Results: CRCs were diagnosed in 447 patients during the study period. The cumulative reflex MSI testing rate was 35.1% (157/447), and 24.2% of those patients tested had MSI-H CRCs (38/157). In groups A, B & C respectively, the rate of reflex MSI testing was 32.2% (92/286), 41.9% (26/62), and 38.1% (37/97). MSI-H was identified in groups A, B, and C at a rate of 28.2% (26/92), 19.2% (5/26). and 18.9% (7/37), respectively. The number of MSI-H CRCs with non-hMLH-1 loss by immunohistochemistry, and therefore strongly implicating LS, for groups A-C were 5 (19.2)%, 1 (20%), and 3 (42.8%), respectively.
Conclusions: A significant number of probable LS patients (5/9; 55.5%) were ≥60 years in the above testing paradigm based on MSI-H phenotype CRC morphology and age. Therefore, guideline #3 of the revised Bethesda guidelines, which recommends testing CRCs with the MSI-H histology diagnosed in a patient who is <60 years, proved inadequate for LS screening in our patient population. Adherence by pathologists to the revised Bethesda guidelines, which recommend testing all CRCs in patients younger than 50 and CRCs with the MSI-H histology in a patient between 50-59 years deserves further consideration, as our practice-based data show that 55.5% of probable LS patients were ≥ 60 years.
Category: Gastrointestinal

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 105, Monday Morning


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