Universal screening to identify Lynch syndrome: two years of experience in a Northern Italian Center.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Cohort Studies
Colon
/ pathology
Colorectal Neoplasms, Hereditary Nonpolyposis
/ diagnosis
DNA Mismatch Repair
Early Detection of Cancer
/ methods
Female
Germ-Line Mutation
Humans
Immunohistochemistry
Incidence
Italy
/ epidemiology
Male
Middle Aged
Rectum
/ pathology
Journal
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)
ISSN: 1473-5709
Titre abrégé: Eur J Cancer Prev
Pays: England
ID NLM: 9300837
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
pubmed:
15
10
2019
medline:
10
7
2021
entrez:
15
10
2019
Statut:
ppublish
Résumé
Lynch syndrome is caused by germline mutations of genes affecting the mismatch repair proteins MLH1, MSH2, MSH6 or PMS2. Identification of Lynch syndrome patients using germline molecular testing in colorectal cancer (CRC) affected patients and in their healthy relatives is a cost-effective model of cancer prevention. Several studies demonstrate that universal tumor testing using immunohistochemical (IHC) analysis of CRC samples is the most efficient approach to identifying patients affected by Lynch syndrome. We studied a cohort of 352 consecutive CRCs for MSH2, MLH1, MSH6 and PMS2 protein expression using universal IHC screening. IHC mismatch repair (MMR) defects were identified in 70 out of 352 cases (19.8%) including six CRCs MSH2/MSH6 defective, two CRCs, respectively, MSH6 and PMS2 defective, 58 CRCs MLH1/PMS2 defective and four CRCs showing atypical MMR pattern. MLH1 promoter methylation and V600E BRAF mutation analysis were investigated on 61 CRCs. Cancer genetic counseling was offered to all 68 patients affected by MMR defective CRCs and 25 patients opted in to this service (36.8% compliance). Pathogenetic variants of MSH2 genes were identified in two cases (55 and 79 years old). Universal screening based on an IHC approach showed a Lynch syndrome incidence of 1/173. The protocol recommended by regional law improved patient compliance. This study demonstrates that the IHC approach for both MMR deficiency and V600E BRAF mutation detections is the most efficient approach for Lynch syndrome screening in the Italian population.
Identifiants
pubmed: 31609810
doi: 10.1097/CEJ.0000000000000543
pii: 00008469-202007000-00001
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
281-288Références
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