Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma.
Gut
; 66(1): 97-106, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-26475632
ABSTRACT
OBJECTIVE:
Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/carcinoma to better define their features and the pathways by which they progress to carcinoma.DESIGN:
A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI pathology practice was conducted. Samples were examined for BRAF and KRAS mutations, the CpG island methylator phenotype (CIMP) and immunostained for MLH1, p53, p16, ß-catenin and 0-6-methylguanine DNA methyltransferase (MGMT).RESULTS:
The median polyp size was 9â mm and 86.5% were proximal. Most were BRAF mutated (92.7%) and 94.0% showed CIMP. Mismatch repair deficiency, evidenced by loss of MLH1 (74.5%) is associated with older age (76.7 versus 71.0; p<0.0029), female gender (70% versus 36%; p<0.0008), proximal location (91% versus 72%; p<0.02), CIMP (98% versus 80%; p<0.02) and lack of aberrant p53 (7% versus 34%; p<0.001) when compared with the mismatch repair-proficient cases. Loss of p16 (43.1%) and gain of nuclear ß-catenin (55.5%) were common in areas of dysplasia/cancer, irrespective of mismatch repair status.CONCLUSIONS:
SSAs containing dysplasia/carcinoma are predominantly small (<10â mm) and proximal. The mismatch repair status separates these lesions into distinct clinicopathological subgroups, although WNT activation and p16 silencing are common to both. Cases with dysplasia occur at a similar age to cases with carcinoma. This, together with the rarity of these 'caught in the act' lesions, suggests a rapid transition to malignancy following a long dwell time as an SSA without dysplasia.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Síndromes Neoplásicos Hereditarios
/
Neoplasias Encefálicas
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Carcinoma
/
Neoplasias Colorrectales
/
Adenoma
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Límite:
Aged80
Idioma:
En
Revista:
Gut
Año:
2017
Tipo del documento:
Article
País de afiliación:
Australia