Loss of expression of MLH1 in non-dysplastic crypts is a harbinger of neoplastic progression in sessile serrated adenomas/polyps.
Histopathology
; 75(3): 376-384, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-30974487
ABSTRACT
AIMS:
Dysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non-dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non-dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps. METHODS ANDRESULTS:
Four hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non-dysplastic and dysplastic portions of the polyps. Seventy-one of 400 (18%) SSAs showed loss of MLH1 expression in non-dysplastic crypts. The prevalence of MLH1-deficient non-dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P < 0.0001). When SSAs with MLH1-deficient dysplasia and those with MLH-1-proficient dysplasia were compared, those with MLH1-deficient dysplasia were more likely to have MLH1-deficient non-dysplastic crypts (66% versus 8.1%, P < 0.0001) and a greater number of discrete foci (3.6 foci versus 1.1 foci, P = 0.008). Also, non-dysplastic crypts with loss of MLH1 expression were more likely to be contiguous with the dysplasia when the dysplasia also showed loss of MLH1 expression (26% versus 0%, P = 0.02).CONCLUSIONS:
Our results suggest that loss of MLH1 expression in non-dysplastic crypts in SSAs precedes the development of MLH1-deficient dysplasia and adenocarcinoma, and may be a biomarker of an advanced serrated polyp even in the absence of dysplasia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pólipos do Colo
/
Neoplasias do Colo
/
Pólipos Adenomatosos
/
Proteína 1 Homóloga a MutL
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Histopathology
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Nova Zelândia