Clinical Performance of Original and Revised Bethesda Guidelines for the Identification of MSH2/MLH1 Gene Carriers in Patients with Newly Diagnosed Colorectal Cancer: Proposal of a New and Simpler Set of Recommendations
Authors: Rodríguez-Moranta, Francisco1; Castells, Antoni1; Andreu, Montserrat2; Piñol, Virgínia1; Castellví-Bel, Sergi1; Alenda, Cristina3; Llor, Xavier4; Xicola, Rosa M.4; Jover, Rodrigo5; Payá, Artemio3; Bessa, Xavier2; Balaguer, Francesc1; Cubiella, Joaquin6; Argüello, Lidia7; Morillas, Juan Diego8; Bujanda, Luis9
Source: The American Journal of Gastroenterology, Volume 101, Number 5, May 2006 , pp. 1104-1111(8)
Publisher: Blackwell Publishing
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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. (Am J Gastroenterol 2006;101:1104–1111)Document Type: Research article
DOI: 10.1111/j.1572-0241.2006.00522.x
Affiliations: 1: Department of Gastroenterology, Institut de Malalties Digestives, Hospital Clínic, IDIBAPS*, University of Barcelona 2: Department of Gastroenterology, Hospital del Mar, Barcelona, Catalonia 3: Department of Pathology, Hospital General Universitario de Alicante, Alicante 4: Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia 5: Department of Gastroenterology, Hospital General Universitario de Alicante, Alicante 6: Department of Gastroenterology, Hospital Cristal Piñor, Ourense 7: Department of Gastroenterology, Hospital Universitario La Fe, Valencia 8: Department of Gastroenterology, Hospital 12 de Octubre, Madrid 9: Department of Gastroenterology, Hospital Donostia, San Sebastián, Spain
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