Serrated Polyps and Serrated Polyposis Syndrome

Ashburn, Jean; Plesec, Thomas; Kalady, Matthew F.

doi:10.1055/s-0036-1584088

Cited by 12 publications

(4 citation statements)

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“…For each lesion, patient and polyp characteristics were retrieved from the electronic medical charts. Rate of progression [low-grade dysplasia (LGD), high-grade dysplasia (HGD), or cancer] was reviewed based on the 2010 edition of the World Health Organization Classification of Tumours of the digestive system [18]. All included lesions were stained for MLH1, SMAD4 and p53, as described previously [5,8].…”

Section: Study Design and Case Selectionmentioning

confidence: 99%

Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite‐instable colorectal cancers

van Toledo,

Bleijenberg,

Venema

et al. 2024

The Journal of Pathology CR

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Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite‐stable and microsatellite‐instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes. We studied a cohort of 23 SSLs with a small focus (<10 mm) of dysplasia or cancer, 10 of which were MLH1 deficient and 13 MLH1 proficient. By comparing, for each SSL, the methylation status of (1) the region of dysplasia or cancer (SSL‐D), (2) the nondysplastic SSL (SSL), and (3) adjacent normal mucosa, differentially methylated probes (DMPs) and regions (DMRs) were assessed both genome‐wide as well as in a tumor‐suppressor gene‐focused approach. By comparing DNAm of MLH1‐deficient SSL‐Ds with their corresponding SSLs, we identified five DMRs, including those annotating for PRDM2 and, not unexpectedly, MLH1. PRDM2 gene promotor methylation was associated with MLH1 expression status, as it was largely hypermethylated in MLH1‐deficient SSL‐Ds and hypomethylated in MLH1‐proficient SSL‐Ds. Significantly increased DNAm levels of PRDM2 and MLH1, in particular at ‘critical’ MLH1 probe sites, were to some extent already visible in SSLs as compared to normal mucosa (p = 0.02, p = 0.01, p < 0.0001, respectively). No DMRs, nor DMPs, were identified for SSLs destined to evolve into MLH1‐proficient SSL‐Ds. Our data indicate that, within both arms of the serrated CRC pathway, the majority of the epigenetic alterations are introduced early during SSL formation. Promoter hypermethylation of PRDM2 and MLH1 on the other hand specifically initiates in SSLs destined to transform into MLH1‐deficient CRCs suggesting that the fate of SSLs may not necessarily result from a stochastic process but possibly is already imprinted and predisposed.

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Section: Study Design and Case Selectionmentioning

confidence: 99%

Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite‐instable colorectal cancers

van Toledo,

Bleijenberg,

Venema

et al. 2024

The Journal of Pathology CR

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“…(8)(9)(10)(11)(12) La OMS ha clasificado las lesiones serradas en: pólipos hiperplásicos, adenomas/pólipos serrados sésiles (ASS) y adenomas serrados tradicionales (AST), con diferentes potenciales de malignización. (13) La detección de estas lesiones es un desafío, debido a su apariencia sutil, y a http://dx.doi.org/10.47892/rgp.2023.431.1466 -Comparador: Colonoscopia convencional de alta definición (sin aditamentos).…”

Section: Introductionunclassified

Intervenciones endoscópicas para mejorar la tasa de detección de lesiones serradas durante la colonoscopia

Pérez

2023

Rev Gastroenterol Peru

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El cáncer colorrectal (CCR) es una de las causas más frecuentes de mortalidad por cáncer en el mundo. Las lesiones serradas son responsables de 10 a 20% de todos los CCR. Los pólipos serrados, en particular los adenomas serrados sésiles (ASS) y adenomas serrados tradicionales (AST), tienen una apariencia sutil y localización proximal, y por ello presentan una alta tasa de lesiones perdidas. El objetivo de la presente revisión fue evaluar la evidencia disponible sobre el uso de diversas intervenciones mejorar la tasa de detección de las lesiones serradas, para de esta forma, disminuir la mortalidad relacionada al CCR.

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“…The underlying mutation leading to CRC through this pathway include mutations in KRAS and BRAF genes as opposed to a mutation in the APC gene that leads to interval CRC through traditional pathway 2. The World Health Organization (WHO) has classified the serrated polyps as following: hyperplastic polyps (HPs), sessile serrated polyps (SSPs), and traditional serrated adenoma 3. These polyps have demonstrated varying malignant potential and can be difficult to detect owing to their often subtle, flat appearance 4–6.…”

mentioning

confidence: 99%

“…2 The World Health Organization (WHO) has classified the serrated polyps as following: hyperplastic polyps (HPs), sessile serrated polyps (SSPs), and traditional serrated adenoma. 3 These polyps have demonstrated varying malignant potential and can be difficult to detect owing to their often subtle, flat appearance. [4][5][6] Meta-analyses have demonstrated improved adenoma detection rates (ADRs) using different technique (dual observers, dynamic position change, wateraided methods, and bowel preparation) and/or adjunct modalities (distal attachments and electronic chromoendoscopy) during colonoscopy.…”

mentioning

confidence: 99%

Do Water-aided Techniques Improve Serrated Polyp Detection Rate During Colonoscopy?

Aziz¹,

Mehta

Weissman

et al. 2020

Journal of Clinical Gastroenterology

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Background and Study Aims: The utility of water-aided techniques (WT): water exchange (WE) and water immersion (WI) have been studied extensively in the literature for improving colonoscopy outcome metrics such as adenoma detection rate. Serrated polyps owing to their location and appearance have a high miss rate. The authors performed a systematic review and meta-analysis of studies comparing WT with the standard gas-assisted (GA) method to determine if there was any impact on serrated polyp detection rate (SPDR) and sessile serrated polyp detection rate.Methods: The following databases were queried for this systematic review: Medline, EMBASE, Cochrane Library, CINAHL, and Web of Sciences. The authors only included randomized controlled trials (RCTs). The primary outcome was SPDR and secondary outcomes were sessile serrated polyp detection rate and cecal intubation rate. Risk ratios (RRs) were calculated for each outcome. A P-value <0.05 was considered to be statistically significant.Results: A total of 4 RCTs (5 arms) with 5306 patients (2571 in the GA group and 2735 in the WT group) were included. The SPDR was significantly increased for the WT group compared with GA (6.1% vs. 3.8%; RR, 1.63; 95% confidence interval, 1.24-2.13; P < 0.001; I 2 = 22.7%). A subgroup analysis for WE technique also demonstrated improved SPDR compared with the GA method (4.9% vs. 3.2%; RR, 1.57; 95% confidence interval, 1.15-2.14; P = 0.004; I 2 = 6.1%).Conclusions: WT, particularly, the WE method results in improved SPDR. This technique should be encouraged in a clinical setting to detect these polyps to prevent interval colorectal cancer.

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Serrated Polyps and Serrated Polyposis Syndrome

Cited by 12 publications

References 50 publications

Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite‐instable colorectal cancers

Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite‐instable colorectal cancers

Intervenciones endoscópicas para mejorar la tasa de detección de lesiones serradas durante la colonoscopia

Do Water-aided Techniques Improve Serrated Polyp Detection Rate During Colonoscopy?

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