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Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer.
JAMA 2005; 293(16):1986-94JAMA

Abstract

CONTEXT

The selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability.

OBJECTIVE

To establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers.

DESIGN, SETTING, AND PATIENTS

A prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001.

INTERVENTIONS

Microsatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline testing.

MAIN OUTCOME MEASURES

Effectiveness and efficiency of both microsatellite instability testing and immunostaining, either directly or previous selection of patients according to the revised Bethesda guidelines, were evaluated with respect to the presence of MSH2/MLH1 germline mutations.

RESULTS

Two hundred eighty-seven patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4%) had a mismatch repair deficiency, with tumors exhibiting either microsatellite instability (n = 83) or loss of protein expression (n = 81). Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1 (4 cases) genes. Strategies based on either microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity, 98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001).

CONCLUSION

The revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC. In patients fulfilling these criteria, both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations.

Authors+Show Affiliations

Department of Gastroenterology, Institut de Malalties Digestives, Hospital Clínic, University of Barcelona, Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15855432

Citation

Piñol, Virgínia, et al. "Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer." JAMA, vol. 293, no. 16, 2005, pp. 1986-94.
Piñol V, Castells A, Andreu M, et al. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005;293(16):1986-94.
Piñol, V., Castells, A., Andreu, M., Castellví-Bel, S., Alenda, C., Llor, X., ... Bessa, X. (2005). Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA, 293(16), pp. 1986-94.
Piñol V, et al. Accuracy of Revised Bethesda Guidelines, Microsatellite Instability, and Immunohistochemistry for the Identification of Patients With Hereditary Nonpolyposis Colorectal Cancer. JAMA. 2005 Apr 27;293(16):1986-94. PubMed PMID: 15855432.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. AU - Piñol,Virgínia, AU - Castells,Antoni, AU - Andreu,Montserrat, AU - Castellví-Bel,Sergi, AU - Alenda,Cristina, AU - Llor,Xavier, AU - Xicola,Rosa M, AU - Rodríguez-Moranta,Francisco, AU - Payá,Artemio, AU - Jover,Rodrigo, AU - Bessa,Xavier, AU - ,, PY - 2005/4/28/pubmed PY - 2005/4/30/medline PY - 2005/4/28/entrez SP - 1986 EP - 94 JF - JAMA JO - JAMA VL - 293 IS - 16 N2 - CONTEXT: The selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite instability. OBJECTIVE: To establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001. INTERVENTIONS: Microsatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors exhibited microsatellite instability and/or lack of protein expression underwent MSH2/MLH1 germline testing. MAIN OUTCOME MEASURES: Effectiveness and efficiency of both microsatellite instability testing and immunostaining, either directly or previous selection of patients according to the revised Bethesda guidelines, were evaluated with respect to the presence of MSH2/MLH1 germline mutations. RESULTS: Two hundred eighty-seven patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients (7.4%) had a mismatch repair deficiency, with tumors exhibiting either microsatellite instability (n = 83) or loss of protein expression (n = 81). Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1 (4 cases) genes. Strategies based on either microsatellite instability testing or immunostaining previous selection of patients according to the revised Bethesda guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity, 98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the revised Bethesda guidelines as the most discriminating set of clinical parameters (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001). CONCLUSION: The revised Bethesda guidelines constitute a useful approach to identify patients at risk for HNPCC. In patients fulfilling these criteria, both microsatellite instability testing and immunostaining are equivalent and highly effective strategies to further select those patients who should be tested for MSH2/MLH1 germline mutations. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/15855432/Accuracy_of_revised_Bethesda_guidelines_microsatellite_instability_and_immunohistochemistry_for_the_identification_of_patients_with_hereditary_nonpolyposis_colorectal_cancer_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.293.16.1986 DB - PRIME DP - Unbound Medicine ER -