Optimizing the detection of hereditary non-polyposis colorectal cancer: An update

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is a dominant inherited disease and accounts for up to 5% of all colorectal cancer (CRC) patients. Despite the optimization of selection criteria and enhancements in molecular techniques for identifying more families with HNPCC, most cases are not recognized. Poor patient recollection of family history and inadequate family history-taking are main causative factors. We propose a new strategy for detecting HNPCC, one in which the pathologist selects patients for microsatellite instability (MSI) testing. Criteria for MSI analysis are: (1) CRC before the age of 50 years, (2) second CRC before 70 years, (3) CRC and HNPCC-associated cancer before 70 years, or (4) adenoma before 40 years. Additionally, patients with a positive MSI test and patients with a positive family history are offered referral for genetic counselling. With this strategy, at least twice the number of HNPCC patients will be identified among a population of CRC patients, and in a cost-effective, efficient and feasible way. The identification of patients with HNPCC is important because intensive surveillance can prevent death from CRC.

A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory

“…These criteria, known as MIPA criteria, simplify the Bethesda guidelines in such a way that pathologists, without knowledge of family history, can easily apply them. These criteria were found to be effective, efficient and feasible in daily practice [41, 42].…”

On the advent of MSI testing of all colorectal cancers and a substantial part of other Lynch syndrome-related neoplasms

“…PALGA is the nationwide network and registry of histopathology and cytopathology in The Netherlands [103] from which diagnostic (e.g., neoplasm diagnostics and multiple LS-associated neoplasms within one patient) and patient information (e.g., age) can be retrieved. Thanks to the simplicity of the criteria, the central role of only one medical professional (the pathologist) and the alert function of the PALGA, these criteria appear to be very effective, efficient and feasible in daily practice [14].…”

“…After evaluation of this strategy, new criteria for the detection of LS (known as MIPA criteria) were implemented nationwide in The Netherlands in 2008. Within these guidelines, the pathologist selects newly diagnosed patients fulfilling one of the following criteria for MMR-deficiency testing (MSI and IHC for four MMR proteins and, on indication, MLH1 promoter methylation and/ or BRAF mutation): CRC or endometrial cancer before the age of 50 years, or CRC with a second synchronous or metachronous CRC or other LS-associated tumor before the age of 70 years [14,102]. These MIPA criteria simplify the Bethesda guidelines in such a way that pathologists, without knowledge of family history, can easily apply them.…”