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Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer.
Gut 2012; 61(6):865-72Gut

Abstract

BACKGROUND

The selection of patients for genetic testing to rule out Lynch syndrome is currently based on fulfilment of at least one of the revised Bethesda criteria followed by mismatch repair (MMR) status analysis. A study was undertaken to compare the present approach with universal MMR study-based strategies to detect Lynch syndrome in a large series of patients with colorectal cancer (CRC).

METHODS

2093 patients with CRC from the EPICOLON I and II cohorts were included. Immunohistochemistry for MMR proteins and/or microsatellite instability (MSI) analysis was performed in tumour tissue. Germline MLH1 and MSH2 mutation analysis was performed in patients whose tumours showed loss of MLH1 or MSH2 staining, respectively. MSH6 genetic testing was done in patients whose tumours showed lack of MSH6 expression or a combined lack of MSH2 and MSH6 expression but did not have MSH2 mutations. PMS2 genetic testing was performed in patients showing isolated loss of PMS2 expression. In patients with MSI tumours and normal or not available MMR protein expression, all four MMR genes were studied.

RESULTS

A total of 180 patients (8.6%) showed loss of expression of some of the MMR proteins and/or MSI. Four hundred and eighty-six patients (23.2%) met some of the revised Bethesda criteria. Of the 14 (0.7%) patients who had a MMR gene mutation, 12 fulfilled at least one of the revised Bethesda criteria and two (14.3%) did not.

CONCLUSIONS

Routine molecular screening of patients with CRC for Lynch syndrome using immunohistochemistry or MSI has better sensitivity for detecting mutation carriers than the Bethesda guidelines.

Authors+Show Affiliations

Unidad de Investigación, Hospital General Universitario, Alicante, 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 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)

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

Language

eng

PubMed ID

21868491

Citation

Pérez-Carbonell, Lucía, et al. "Comparison Between Universal Molecular Screening for Lynch Syndrome and Revised Bethesda Guidelines in a Large Population-based Cohort of Patients With Colorectal Cancer." Gut, vol. 61, no. 6, 2012, pp. 865-72.
Pérez-Carbonell L, Ruiz-Ponte C, Guarinos C, et al. Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. Gut. 2012;61(6):865-72.
Pérez-Carbonell, L., Ruiz-Ponte, C., Guarinos, C., Alenda, C., Payá, A., Brea, A., ... Jover, R. (2012). Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. Gut, 61(6), pp. 865-72. doi:10.1136/gutjnl-2011-300041.
Pérez-Carbonell L, et al. Comparison Between Universal Molecular Screening for Lynch Syndrome and Revised Bethesda Guidelines in a Large Population-based Cohort of Patients With Colorectal Cancer. Gut. 2012;61(6):865-72. PubMed PMID: 21868491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer. AU - Pérez-Carbonell,Lucía, AU - Ruiz-Ponte,Clara, AU - Guarinos,Carla, AU - Alenda,Cristina, AU - Payá,Artemio, AU - Brea,Alejandro, AU - Egoavil,Cecilia M, AU - Castillejo,Adela, AU - Barberá,Victor M, AU - Bessa,Xavier, AU - Xicola,Rosa M, AU - Rodríguez-Soler,María, AU - Sánchez-Fortún,Cristina, AU - Acame,Nuria, AU - Castellví-Bel,Sergi, AU - Piñol,Virgínia, AU - Balaguer,Francesc, AU - Bujanda,Luis, AU - De-Castro,María-Luisa, AU - Llor,Xavier, AU - Andreu,Montserrat, AU - Carracedo,Angel, AU - Soto,José-Luis, AU - Castells,Antoni, AU - Jover,Rodrigo, Y1 - 2011/08/25/ PY - 2011/8/27/entrez PY - 2011/8/27/pubmed PY - 2012/7/14/medline SP - 865 EP - 72 JF - Gut JO - Gut VL - 61 IS - 6 N2 - BACKGROUND: The selection of patients for genetic testing to rule out Lynch syndrome is currently based on fulfilment of at least one of the revised Bethesda criteria followed by mismatch repair (MMR) status analysis. A study was undertaken to compare the present approach with universal MMR study-based strategies to detect Lynch syndrome in a large series of patients with colorectal cancer (CRC). METHODS: 2093 patients with CRC from the EPICOLON I and II cohorts were included. Immunohistochemistry for MMR proteins and/or microsatellite instability (MSI) analysis was performed in tumour tissue. Germline MLH1 and MSH2 mutation analysis was performed in patients whose tumours showed loss of MLH1 or MSH2 staining, respectively. MSH6 genetic testing was done in patients whose tumours showed lack of MSH6 expression or a combined lack of MSH2 and MSH6 expression but did not have MSH2 mutations. PMS2 genetic testing was performed in patients showing isolated loss of PMS2 expression. In patients with MSI tumours and normal or not available MMR protein expression, all four MMR genes were studied. RESULTS: A total of 180 patients (8.6%) showed loss of expression of some of the MMR proteins and/or MSI. Four hundred and eighty-six patients (23.2%) met some of the revised Bethesda criteria. Of the 14 (0.7%) patients who had a MMR gene mutation, 12 fulfilled at least one of the revised Bethesda criteria and two (14.3%) did not. CONCLUSIONS: Routine molecular screening of patients with CRC for Lynch syndrome using immunohistochemistry or MSI has better sensitivity for detecting mutation carriers than the Bethesda guidelines. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/21868491/Comparison_between_universal_molecular_screening_for_Lynch_syndrome_and_revised_Bethesda_guidelines_in_a_large_population_based_cohort_of_patients_with_colorectal_cancer_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=21868491 DB - PRIME DP - Unbound Medicine ER -