Search

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. [ABSTRACT FROM AUTHOR]

Background and Aim: Serrated polyps have been recognized as a premalignant lesion accounting for a significant proportion of colorectal cancer. Limited data are available regarding the risk factors for colorectal sessile serrated lesions (SSLs). We aimed to investigate clinical risk factors of SSLs and compared them with colorectal adenomas in a study population of Chinese individuals. Methods: A retrospective case–control study was performed in an academic tertiary‐referral center in Hong Kong. Subjects with SSLs and adenomas were identified from the hospital pathology database from January 2010 to December 2020, and additional clinical data were retrieved from the electronic patient record system. We compared clinical features and risk factors of SSL patients with those without these lesions. Results: A total of 2295 subjects were included in the study, including 459 subjects with SSLs, 918 subjects with adenomas, and 918 subjects with normal colonoscopy. By multivariable logistic regression, compared with normal subjects, patients with SSLs only were significantly more likely to have dyslipidemia (adjusted OR: 1.431, 95% CI 1.008–2.030) and diabetes mellitus (adjusted OR: 2.119, 95% CI 1.439–3.122). Conclusions: Dyslipidemia and diabetes were independent risk factors for SSLs. Our findings suggest these metabolic factors may be important for the risk of SSLs. The findings may improve our understanding of SSLs and shed light on patient selection for screening and risk stratification. [ABSTRACT FROM AUTHOR]

Sessile serrated lesions (SSLs) and microvesicular hyperplastic polyps (MVHPs) are colorectal lesions displaying gastric differentiation. Griffonia simplicifolia‐II (GS‐II) is a lectin specific to terminal α/βGlcNAc residues. Here, we assessed GS‐II binding and performed immunostaining for HIK1083 (specific to terminal αGlcNAc residues), MUC5AC, MUC6, and special AT‐rich sequence binding protein 2 (SATB2) in SSLs, MVHPs, and tubular adenomas (TAs). We observed MUC5AC positivity in 28 of 30 SSLs, but in only three of 23 TAs. Moreover, 24 of 30 SSLs were MUC6‐positive, while none of the 23 TAs were MUC6‐positive. None of the 30 SSLs or 23 TAs showed HIK1083 positivity. All 30 SSLs and 26 MVHPs were GS‐II‐positive, while only seven of 23 were in TAs. GS‐II staining was mainly distributed in the Golgi region, but SSLs and MVHPs showed goblet cell distribution, in 20 of 30 and 19 of 26 cases, respectively. All SSLs, MVHPs, and TAs were SATB2‐positive, but 21 of 30 SSLs and 12 of 26 MVHPs showed decreased staining intensity relative to adjacent mucosa, a decrease seen in only two of 23 in TAs. These results indicate overall that increased terminal βGlcNAc and decreased SATB2 expression are characteristics of SSLs and MVHPs. [ABSTRACT FROM AUTHOR]

Background and Aim: Sessile serrated lesions (SSLs) act as precursors to colorectal cancer, sometimes harbor carcinomas, and are sometimes incompletely resected. We aimed to evaluate local recurrence after endoscopic resection of SSL ≥10 mm. Methods: This prospective, single‐arm, observational study was performed at eight Japanese tertiary institutions. Colorectal lesions ≥10 mm were resected endoscopically, and the pathological diagnosis was either an SSL or hyperplastic polyp (HP). Follow‐up colonoscopy was performed 1 year later, and the local recurrence was evaluated by biopsy. Results: From October 2018 to September 2021, 104 cases with 123 lesions were registered. Among the pathologically diagnosed 105 SSLs and 18 HPs, 95 and 7 lesions were diagnosed as SSLs and HPs, respectively, by central pathological review. Among the 104 endoscopically diagnosed SSLs, 86 were diagnosed as SSLs, whereas among the 11 endoscopically diagnosed HPs, two were diagnosed as HPs by central pathological review (the rest were SSLs). Among the 95 patients with 113 lesions who underwent follow‐up colonoscopy, resection scars were identified in 95 (84%) lesions. Three (3.1%; 95% confidence interval 0.6–8.7%) local recurrences were diagnosed pathologically among 98 pathologically diagnosed SSLs. Two (6%) local recurrences were diagnosed in patients with SSLs ≥20 mm. Conclusions: The local recurrence rate after endoscopic resection of SSLs ≥10 mm was 3.1%. Careful follow‐up is recommended after endoscopic resection of large SSLs. Endoscopically diagnosed HPs ≥10 mm were sometimes pathologically diagnosed as SSL and should be considered for resection. [ABSTRACT FROM AUTHOR]

Background and Aim: The reported prevalence and risk factors for sessile serrated lesions (SSLs) show significant variation. We aimed to specifically study the prevalence and potential risk factors of SSLs in an average risk colorectal cancer (CRC) screening population of Chinese subjects. Methods: This is a case–control study of prospectively collected data from a territory‐wide colorectal screening program in Hong Kong. Information on risk factors was obtained from questionnaires completed prior to screening colonoscopy. We compared subjects with SSLs against controls without these lesions to identify potential risk factors using multivariable logistic regression. Results: Of 12 039 asymptomatic screening subjects, 6011 subjects received a screening colonoscopy with 2214 subjects (36.8%) having conventional adenomas, 486 subjects (8.1%) having hyperplastic polyps, and 85 subjects (1.4%) having SSLs only. Of these subjects, three had synchronous advanced adenomas and were excluded from the analysis. More than 60% of these lesions were in the proximal colon. We compared these 82 subjects with SSLs only and 3226 controls without any polyps. After multivariable logistic regression, age ≥ 66 years, smoking, and diabetes mellitus (DM) were significant independent risk factors for SSLs. Conclusion: In this study, we report the prevalence of SSLs to be 1.4%. Age ≥ 66 years, smoking, and DM were independent risk factors for these lesions. Our findings provide relevant new data that should be taken into consideration when designing region‐specific surveillance programs for SSLs with the ultimate goal of reducing the risk of CRC. [ABSTRACT FROM AUTHOR]