Clinical Performance of Original and Revised Bethesda Guidelines for the Identification of MSH2/MLH1 Gene Carriers in Patients with Newly Diagnosed ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-05

AUTHORS

Francisco Rodríguez-Moranta, Antoni Castells, Montserrat Andreu, Virgnia Piñol, Sergi Castellví-Bel, Cristina Alenda, Xavier Llor, Rosa M Xicola, Rodrigo Jover, Artemio Payá, Xavier Bessa, Francesc Balaguer, Joaquin Cubiella, Lidia Argüello, Juan Diego Morillas, Luis Bujanda

ABSTRACT

Identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is a critical and difficult issue. For this purpose, the National Cancer Institute outlined a set of recommendations, the Bethesda guidelines, which have recently been revised. OBJECTIVE: To compare the clinical performance of original and revised Bethesda guidelines for the detection of MSH2/MLH1 gene carriers in patients with colorectal cancer. METHODS: A total of 1,222 patients with newly diagnosed colorectal cancer were included in the EPICOLON study, a prospective, multicenter, nationwide epidemiology survey aimed at establishing the incidence of HNPCC in Spain (JAMA 2005; 293:1986-1994). Performance characteristics of the original and revised Bethesda guidelines were assessed with respect to the presence of MSH2/MLH1 germline mutations. Logistic regression analysis was performed to establish the most effective strategy. RESULTS: Original or revised Bethesda guidelines were equivalent strategies in terms of sensitivity (100%vs 100%; ns), specificity (98.1%vs 97.9%; ns), and overall accuracy (98.1%vs 97.9%; ns), as well as positive (25.8%vs 24.2%) and negative predictive values (100%vs 100%). The most discriminating individual variables were criteria number 1 (i.e., fulfillment of the Amsterdam criteria; RR = 34.14; 95% CI = 6.85-170.16; p < 0.001) and number 2 (i.e., individuals with two HNPCC-related neoplasms; RR = 35.63; 95% CI = 4.83-262.6; p < 0.001) of the original guidelines, and criterion number 1 of the revised guidelines (i.e., colorectal cancer diagnosed under 50 yr of age; RR = 29.34; 95% CI = 3.81-225.96; p= 0.001). The aggregation of these three criteria was equivalent to both Bethesda guidelines in terms of sensitivity (100%) and negative predictive value (100%), but superior to the revised criteria regarding specificity (98.5%; p < 0.05), overall accuracy (98.5%; p < 0.05), and positive predictive value (30.8%). CONCLUSIONS: Original and revised Bethesda guidelines are equivalent, highly effective criteria for the identification of MSH2/MLH1 gene mutation carriers in patients with newly diagnosed colorectal cancer. A new set of recommendations, based on a combination of some of their individual criteria, may provide additional advantages in terms of effectiveness. More... »

PAGES

ajg2006204

Identifiers

URI

http://scigraph.springernature.com/pub.10.1111/j.1572-0241.2006.00522.x

DOI

http://dx.doi.org/10.1111/j.1572-0241.2006.00522.x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034727602

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16696788


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