Endoscopic and molecular characterization of colorectal sessile serrated adenoma/polyps with cytologic dysplasia

Tanaka, Yoshihito; Yamano, Hiro‐o; Yamamoto, Eiko; Matushita, Hiro-o; Aoki, Hironori; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Nakaoka, Michiko; Yoshida, Yuko; Eizuka, Makoto; Sugai, Tamotsu; Suzuki, Hiromu; Nakase, Hiroshi

doi:10.1016/j.gie.2017.05.006

Cited by 28 publications

(28 citation statements)

References 24 publications

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“…Although previous studies have reported SSA/Ps‐CD(+) in older female patients and in the proximal colon, there were no significant differences between SSA/Ps‐CD(−) and SSA/Ps‐CD(+) in this study. However, endoscopic morphological findings, such as large or small nodules on the surface and partial protrusion of the lesions, were significantly more common in SSA/Ps‐CD(+) than in SSA/Ps‐CD(−) (46.2% vs 2.7%, P < 0.01).…”

Section: Discussioncontrasting

confidence: 97%

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Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with cytological dysplasia

Sano¹,

Fujimori

Ichikawa

et al. 2018

J of Gastro and Hepatol

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Section: Discussioncontrasting

confidence: 97%

“…Conversely, recent evidence has suggested that SSA/Ps may rapidly progress to carcinomas after they start to develop cytological dysplasia (CD) . Accordingly, several recent studies have attempted to endoscopically predict CD within SSA/Ps …”

Section: Introductionmentioning

confidence: 99%

Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with cytological dysplasia

Sano¹,

Fujimori

Ichikawa

et al. 2018

J of Gastro and Hepatol

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“…SSA/Ps with cytological dysplasia are reportedly characterized by frequent MLH1 methylation and are at a high risk of developing into CRC [8]. We found that the Type II-O plus Type III/IV pit pattern is a common feature of SSA/Ps with cytological dysplasia in both the proximal and distal colon [9], which suggests that progression of SSA/Ps to more advanced lesions is associated with further accumulation of molecular alterations and morphological changes.…”

Section: Associations Between Microsurface Structures and Molecular Amentioning

confidence: 59%

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis

et al. 2018

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Background: Colorectal cancers (CRCs) develop through the accumulation of genetic and epigenetic alterations of oncogenes and tumor suppressor genes. In addition to the well-characterized adenoma-carcinoma sequence, the serrated neoplasia pathway is now recognized as an alternative pathway for CRC development. Summary: Through analysis of the colonoscopic, pathological, and molecular features of colorectal tumors, we identified a novel microsurface structure characteristic of serrated lesions. The Type II-Open (Type II-O) pit pattern is highly specific to sessile serrated adenoma/polyps (SSA/Ps), and Type-II-O-positive tumors frequently exhibit v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and 5′-C-phosphate-G-3′ (CpG) island hypermethylation. By screening DNA methylation associated with the development of serrated lesions, we detected methylation of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) in traditional serrated adenomas (TSAs). Epigenetic silencing of SMOC1 is prevalent among TSAs but it is rarely observed in SSA/Ps, which suggests SMOC1 could be a useful diagnostic marker of serrated lesions. We also searched for epigenetic alterations associated with the growth pattern of colorectal tumors and found that methylation of neurotensin receptor 1 is associated with lateral and non-invasive tumor growth. Key Message: Through the summarized studies, we have been able to identify novel morphological and molecular features that could contribute to a better understanding of colorectal tumors and to improved clinical diagnosis.

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“…Forty studies assessing 3511 serrated adenomas were included . The whole process of study selection is reported schematically in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…However, more recently some authors have advocated that the cytological changes of TSA are non‐dysplastic . Furthermore, they have differentiated any further dysplasia into ‘serrated’ or ‘conventional’, based on the architecture (saw‐tooth or tubular/villous, respectively) and cytology (eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli, or basophilic cytoplasm and cigar‐shaped nuclei, respectively) . We adopted the latter approach to extract data for the association between BRAF status and dysplasia.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological factors associated with BRAF‐V600E mutation in colorectal serrated adenomas

et al. 2019

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Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF‐V600E mutation in serrated adenomas. Systematic review and meta‐analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF‐V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P‐value <0.05 was considered significant. Forty studies assessing 3511 serrated adenomas (2375 SSAs and 1136 TSAs) were included. BRAF‐V600E mutation was significantly associated with proximal localisation (OR = 2.71; P < 0.00001) and CIMP‐H status (OR = 4.81; P < 0.0001) in both SSA and TSA, with polyp size <10 mm (OR = 0.41; P = 0.02) in TSA, and with endoscopic pit pattern II‐O (OR = 13.11; P < 0.00001) and expression of MUC5A5 (OR = 4.43; P = 0.003) and MUC6 (OR = 2.28; P < 0.05) in SSA. Conversely, BRAF mutation was not associated with age <70 years (OR = 1.63; P = 0.34), age <60 years (OR = 0.86; P = 0.79), female sex (OR = 0.77; P = 0.12), flat morphology (OR = 1.52; P = 0.16), presence of any dysplasia (OR = 1.01; P = 0.59), serrated dysplasia (OR = 1.23; P = 0.72) and invasive cancer (OR = 0.67; P = 0.32), nuclear β‐catenin expression (OR = 0.73; P = 0.21) and p53 overexpression (OR = 1.24; P = 0.82). In conclusion, BRAF‐V600E mutation is associated with proximal localisation and CIMP‐H status in both SSA and TSA, with size <10 mm only in TSA, and with expression of MUC5A5 and MUC6 and endoscopic pit pattern II‐O at least in SSA. In serrated adenomas, BRAF‐V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component.

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Endoscopic and molecular characterization of colorectal sessile serrated adenoma/polyps with cytologic dysplasia

Cited by 28 publications

References 24 publications

Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with cytological dysplasia

Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with cytological dysplasia

Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis

Clinicopathological factors associated with BRAF‐V600E mutation in colorectal serrated adenomas

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