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Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening.
Am J Gastroenterol. 2008 Nov; 103(11):2825-35; quiz 2836.AJ

Abstract

BACKGROUND

The identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing remains a critical issue. The Bethesda guidelines were developed to preselect patients for microsatellite instability (MSI) testing before germline mutation screening. These criteria have been revised, and a new set of recommendations, the revised Bethesda guidelines, has been proposed.

OBJECTIVE

To evaluate the performance of these revised guidelines for identifying patients with HNPCC in a series of unselected consecutive patients and compare this revised guidelines-based approach with a molecular strategy (MSI testing for all tumors, followed by exclusion of MSI-positive sporadic cases from mutational testing).

PATIENTS AND METHODS

The study included 214 patients with newly diagnosed colorectal cancer. The MSI analysis was performed for all tumors. Germline testing, guided by immunohistochemical staining for mismatch repair proteins, was performed for patients with MSI-positive tumors. Sporadic MSI-positive tumors were identified by screening for BRAF mutation and MLH1 promoter methylation.

RESULTS

Ninety patients (42.1%) met the revised guidelines. Twenty-one patients (9.8%) had MSI-positive tumors. Germline testing identified eight mutations (3.7%) (MSH2 N = 5, MLH1 N = 2, MSH6 N =1). The revised guidelines failed to identify 2 of the 8 probands (aged 67 and 81 yr, both with no family history). In contrast, the molecular strategy identified all patients requiring testing for germline mutation. The percentages of patients selected for germline testing by the revised guidelines and the molecular strategy were 4.2% and 5.1%, respectively.

CONCLUSIONS

The revised Bethesda guidelines did not identify all HNPCC cases in our series. The molecular approach identified all HNPCC patients with MSI-positive tumors, increasing the workload for germline testing only slightly.

Authors+Show Affiliations

Service d'Anatomie et de Cytologie Pathologiques, Hôpital Ambroise Paré, AP-HP, Université Versailles-Saint Quentin en Yvelines, Boulogne, France.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 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18759827

Citation

Julié, Catherine, et al. "Identification in Daily Practice of Patients With Lynch Syndrome (hereditary Nonpolyposis Colorectal Cancer): Revised Bethesda Guidelines-based Approach Versus Molecular Screening." The American Journal of Gastroenterology, vol. 103, no. 11, 2008, pp. 2825-35; quiz 2836.
Julié C, Trésallet C, Brouquet A, et al. Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening. Am J Gastroenterol. 2008;103(11):2825-35; quiz 2836.
Julié, C., Trésallet, C., Brouquet, A., Vallot, C., Zimmermann, U., Mitry, E., Radvanyi, F., Rouleau, E., Lidereau, R., Coulet, F., Olschwang, S., Frébourg, T., Rougier, P., Nordlinger, B., Laurent-Puig, P., Penna, C., Boileau, C., Franc, B., Muti, C., & Hofmann-Radvanyi, H. (2008). Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening. The American Journal of Gastroenterology, 103(11), 2825-35; quiz 2836. https://doi.org/10.1111/j.1572-0241.2008.02084.x
Julié C, et al. Identification in Daily Practice of Patients With Lynch Syndrome (hereditary Nonpolyposis Colorectal Cancer): Revised Bethesda Guidelines-based Approach Versus Molecular Screening. Am J Gastroenterol. 2008;103(11):2825-35; quiz 2836. PubMed PMID: 18759827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification in daily practice of patients with Lynch syndrome (hereditary nonpolyposis colorectal cancer): revised Bethesda guidelines-based approach versus molecular screening. AU - Julié,Catherine, AU - Trésallet,Christophe, AU - Brouquet,Antoine, AU - Vallot,Céline, AU - Zimmermann,Ute, AU - Mitry,Emmanuel, AU - Radvanyi,François, AU - Rouleau,Etienne, AU - Lidereau,Rosette, AU - Coulet,Florence, AU - Olschwang,Sylviane, AU - Frébourg,Thierry, AU - Rougier,Philippe, AU - Nordlinger,Bernard, AU - Laurent-Puig,Pierre, AU - Penna,Christophe, AU - Boileau,Catherine, AU - Franc,Brigitte, AU - Muti,Christine, AU - Hofmann-Radvanyi,Hélène, Y1 - 2008/08/27/ PY - 2008/9/2/pubmed PY - 2009/1/1/medline PY - 2008/9/2/entrez SP - 2825-35; quiz 2836 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 103 IS - 11 N2 - BACKGROUND: The identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing remains a critical issue. The Bethesda guidelines were developed to preselect patients for microsatellite instability (MSI) testing before germline mutation screening. These criteria have been revised, and a new set of recommendations, the revised Bethesda guidelines, has been proposed. OBJECTIVE: To evaluate the performance of these revised guidelines for identifying patients with HNPCC in a series of unselected consecutive patients and compare this revised guidelines-based approach with a molecular strategy (MSI testing for all tumors, followed by exclusion of MSI-positive sporadic cases from mutational testing). PATIENTS AND METHODS: The study included 214 patients with newly diagnosed colorectal cancer. The MSI analysis was performed for all tumors. Germline testing, guided by immunohistochemical staining for mismatch repair proteins, was performed for patients with MSI-positive tumors. Sporadic MSI-positive tumors were identified by screening for BRAF mutation and MLH1 promoter methylation. RESULTS: Ninety patients (42.1%) met the revised guidelines. Twenty-one patients (9.8%) had MSI-positive tumors. Germline testing identified eight mutations (3.7%) (MSH2 N = 5, MLH1 N = 2, MSH6 N =1). The revised guidelines failed to identify 2 of the 8 probands (aged 67 and 81 yr, both with no family history). In contrast, the molecular strategy identified all patients requiring testing for germline mutation. The percentages of patients selected for germline testing by the revised guidelines and the molecular strategy were 4.2% and 5.1%, respectively. CONCLUSIONS: The revised Bethesda guidelines did not identify all HNPCC cases in our series. The molecular approach identified all HNPCC patients with MSI-positive tumors, increasing the workload for germline testing only slightly. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/18759827/Identification_in_daily_practice_of_patients_with_Lynch_syndrome__hereditary_nonpolyposis_colorectal_cancer_:_revised_Bethesda_guidelines_based_approach_versus_molecular_screening_ L2 - http://Insights.ovid.com/pubmed?pmid=18759827 DB - PRIME DP - Unbound Medicine ER -