Lynch syndrome screening in colorectal cancer: results of a prospective 2‐year regional programme validating the NICE diagnostics guidance pathway throughout a 5.2‐million population

Autor: Danny Kaye, Philip Quirke, Nicholas P. West, Niall Gallop, Caroline A. Young, Amy Glover, Scarlet Brockmoeller, Gordon G A Hutchins, Hannah Rossington, Alice C. Westwood
Rok vydání: 2021
Předmět:
Adult
Male
Proto-Oncogene Proteins B-raf
0301 basic medicine
medicine.medical_specialty
Histology
Colorectal cancer
Population
Nice
DNA Mismatch Repair
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Internal medicine
Biomarkers
Tumor
medicine
PMS2
Humans
Genetic Predisposition to Disease
Genetic Testing
Prospective Studies
education
neoplasms
Early Detection of Cancer
Aged
computer.programming_language
education.field_of_study
business.industry
General Medicine
DNA Methylation
Middle Aged
medicine.disease
Colorectal Neoplasms
Hereditary Nonpolyposis
Immunohistochemistry
United Kingdom
digestive system diseases
Lynch syndrome
MSH6
030104 developmental biology
MSH2
030220 oncology & carcinogenesis
Mutation
Medical genetics
Female
Colorectal Neoplasms
MutL Protein Homolog 1
business
computer
Zdroj: Histopathology. 79:690-699
ISSN: 1365-2559
0309-0167
Popis: AIMS Screening all patients newly diagnosed with colorectal cancer (CRC) for possible Lynch syndrome (LS) has been recommended in the United Kingdom since the National Institute for Health and Care Excellence (NICE) released new diagnostics guidance in February 2017. We sought to validate the NICE screening pathway through a prospective regional programme throughout a 5.2-million population during a 2-year period. METHODS AND RESULTS Pathology departments at 14 hospital trusts in the Yorkshire and Humber region of the United Kingdom were invited to refer material from patients with newly diagnosed CRC aged 50 years or over between 1 April 2017 and 31 March 2019 for LS screening. Testing consisted of immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 followed by BRAF mutation analysis ± MLH1 promoter methylation testing in cases showing MLH1 loss. A total of 3141 individual specimens were submitted for testing from 12 departments consisting of 3061 unique tumours and 2791 prospectively acquired patients with CRC. Defective mismatch repair (dMMR) was observed in 15% of cases. In cases showing MLH1 loss, 76% contained a detectable BRAF mutation and, of the remainder, 77% showed MLH1 promoter hypermethylation. Of the patients included in the final analysis, 81 (2.9%) had an indication for germline testing. CONCLUSION LS screening using the NICE diagnostics guidance pathway is deliverable at scale identifying significant numbers of patients with dMMR. This information is used to refer patients to regional clinical genetics services in addition to informing treatment pathways including the use of adjuvant/neoadjuvant chemotherapy and immunotherapy.
Databáze: OpenAIRE
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