Prospective immunohistochemical analysis of primary colorectal cancers for loss of mismatch repair protein expression.
BACKGROUND: Evaluation of patients for Lynch syndrome includes assessment of age and family cancer history as well as testing for microsatellite instability and alterations in mismatch repair (MMR) genes. We examined the value of routine immunohistochemistry (IHC) for MMR proteins in patients with colorectal cancer (CRC) undergoing resection at a single institution. PATIENTS AND METHODS: Beginning in July 2006, all patients aged < 50 years who were undergoing resection of primary CRC had their specimens routinely examined by IHC for MMR proteins. Patients aged 50-60 years were examined if histopathology suggestive of Lynch syndrome was reported, and patients of any age were examined if strong clinical suspicion was present. Family cancer history was analyzed and fulfillment of Amsterdam II criteria determined. RESULTS: Over an 18-month period, 96 patients aged < 50 years underwent CRC resection. Out of these, 72 patients (75%) had immunohistochemical testing, with an overall MMR protein loss rate of 19%. In selected patients aged 50-60 years and > 60 years, loss rates were 26% and 65%, respectively. Of all patients with MMR protein loss, 10 (32%) had reported histopathology, and 3 (10%) had family histories suggesting Lynch syndrome. CONCLUSION: We demonstrate the feasibility of routine immunohistochemical testing for MMR proteins in patients with CRC. As only a minority of patients with MMR protein loss met Amsterdam II criteria or had suggestive histopathology reported, routine IHC may identify patients with Lynch syndrome who might otherwise be missed.