Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer

Abstract

EREDITARY NONPOLYPOSIS COlorectal cancer (HNPCC), also named Lynch syndrome, is an autosomal dominant disorder that accounts for approximately 1% to 3% of all colorectal cancers. 1,2 HNPCC is caused by germline mutations in DNA mismatch repair genes, mainly MSH2 and MLH1. 3 Defects on this pathway lead to changes in the length of nucleotide repeat sequences of tumor DNA, termed microsatellite instability.Although a great advance in the understanding of the molecular basis of HNPCC has taken place in the last decade, optimal selection of individuals for HNPCC genetic testing remains controversial. 4 In 1991, the International See also pp 1979 and 2028.

Performance of clinical guidelines compared with molecular tumour screening methods in identifying possible Lynch syndrome among colorectal cancer patients: a Norwegian population-based study

“…In that perspective, the RBG sensitivity of 50% is disappointingly low. It is noteworthy that our estimate is also low compared with other population-based studies that have reported a sensitivity of B90% for RBG in identifying MSI-H tumours suspicious of being LS associated (Pinol et al, 2005;Vasen et al, 2007). Moreover, our results showed that only 7% of patients who were selected for MSI/ICH testing by the RBG were confirmed as being highly suspicious of LS by molecular tumour testing.…”

“…Most studies of unselected CRC patients have analysed MLH1 and MSH2 genes, as these are most commonly mutated in LS (de la Chapelle, 2004;Domingo et al, 2004;Julie et al, 2008). Pinol et al (2005) performed only IHC and MSI analyses among unselected CRC patients to identify MSH2 and MLH1 germline mutation carriers, whereas we also included molecular analyses for the detection of mutations of MSH6 and PMS2. Many studies have used highly selected groups of CRC patients, or included patients from hereditary cancer clinics (Young et al, 2001;Hitchins et al, 2007) Differences in study design will typically complicate comparisons with the results of population studies.…”

“…Molecular tumour analyses may improve the diagnostic accuracy of LS (Vasen et al, 2007;Julie et al, 2008), and several molecular analyses have been used (Young et al, 2001;Deng et al, 2004;Kambara et al, 2004;Koinuma et al, 2004;Pinol et al, 2005;Imai and Yamamoto, 2008). Immunohistochemistry has the advantage of identifying the underlying MMR gene defect, and germline analyses can be targeted to that specific MMR gene.…”

“…Some studies have restricted the analysis to one marker (Pinol et al, 2005), and others have used some of the markers that we used. The panel of markers recommended by Boland et al (1998) has been used in several studies.…”

Epidemioclinical Feature of Early-Onset Colorectal Cancer at-Risk for Lynch Syndrome in Central Iran

“…(Table 3) Discussion I-Epidemiologic features: This study was designed to find most detectable HNPCC families in Central Iran, since there is a lack of data around the issue in our population. Due to our financial limitations and high family size in Iranian population, we used Amsterdam II Criteria as a more specific tool than revised Bethesda guidelines to screen the early-onset at-risk patients (Syngal et al, 2000;Pinol et al, 2005).…”