Molecular characterization of sessile serrated adenoma/polyps with dysplasia/carcinoma based on immunohistochemistry, next-generation sequencing, and microsatellite instability testing: a case series study

Murakami, Takashi; Akazawa, Yoichi; Yatagai, Noboru; Hiromoto, Takafumi; Sasahara, Noriko; Saito, Tsuyoshi; Sakamoto, Naoto; Nagahara, Akihito; Yao, Takashi

doi:10.1186/s13000-018-0771-3

Cited by 30 publications

(35 citation statements)

References 48 publications

(80 reference statements)

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“…reported that FBXW7 (a tumor‐suppressor gene) mutant colorectal cancers had significant associations with MSI‐high tumors in a large‐scale study of 1519 cases . Furthermore, MSI‐high SSA/Ps with dysplasia or invasive carcinoma harbored an FBXW7 mutation, indicating that FBXW7 mutations might potentially be involved in the progression of MSI‐high serrated lesions.…”

Section: Molecular Characterization Of Sessile Serrated Adenoma/polypmentioning

confidence: 99%

“…Sporadic colorectal cancers with the MSI-high phenotype account for approximately 3-15% of all colorectal cancers. 29 MSI is a unique molecular alteration induced by deficiencies in the DNA-mismatch repair system and is characterized by unstable (variable length) microsatellites, a type of simple DNA 31 Furthermore, MSI-high SSA/Ps with dysplasia or invasive carcinoma harbored an FBXW7 mutation, 16 indicating that FBXW7 mutations might potentially be involved in the progression of MSIhigh serrated lesions. On the contrary, activation of the second arm of the serrated neoplasia pathway, also driven by CpG island methylation of unspecified tumor-suppressor genes but not DNA repair genes, may indicate progression to BRAF-mutant MSS carcinoma.…”

Section: Molecular Characterization Of Sessile Serrated Adenoma/polypmentioning

confidence: 99%

“…Recent studies have shown associations between SSA/Ps and the methylation or loss of protein expression for DNA repair genes such as MLH1 , a CpG island methylator phenotype, BRAF mutations, and a lack of genetic alterations in CTNNB1 , which is the gene that codes for β‐catenin protein . Furthermore, colorectal carcinomas arising in SSA/Ps might reportedly be associated with not only BRAF ‐mutated MSI‐high but also BRAF ‐mutated microsatellite stable (MSS) colorectal carcinomas . In particular, BRAF ‐mutated MSS colorectal carcinomas have a dismal prognosis and an aggressive clinical course with adverse histological features, such as lymphatic and perineural invasion and high tumor budding …”

Section: Introductionmentioning

confidence: 99%

“…15 Furthermore, colorectal carcinomas arising in SSA/Ps might reportedly be associated with not only BRAF-mutated MSI-high but also BRAF-mutated microsatellite stable (MSS) colorectal carcinomas. 16 In particular, BRAF-mutated MSS colorectal carcinomas have a dismal prognosis and an aggressive clinical course with adverse histological features, such as lymphatic and perineural invasion and high tumor budding. 17,18 Some researchers [19][20][21] have suggested that some serrated lesions might progress rapidly to invasive carcinomas.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathological features, diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Murakami

Sakamoto

Nagahara

2019

J of Gastro and Hepatol

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Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.

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Section: Molecular Characterization Of Sessile Serrated Adenoma/polypmentioning

confidence: 99%

Section: Molecular Characterization Of Sessile Serrated Adenoma/polypmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinicopathological features, diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Murakami

Sakamoto

Nagahara

2019

J of Gastro and Hepatol

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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%

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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Integrated genetic and epigenetic analysis of cancer‐related genes in non‐ampullary duodenal adenomas and intramucosal adenocarcinomas

Ota

Sawada

Tsuyama

et al. 2020

The Journal of Pathology

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The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer-related genes in these lesions. One hundred and seven non-ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal-type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric-type tumors (2 pyloric gland adenomas and 5 intramucosal adenocarcinomas), were investigated. Using bisulfite pyrosequencing, we assessed the methylation status of CpG island methylator phenotype (CIMP) markers and MLH1. Then using next-generation sequencing, we performed targeted exome sequence analysis within 75 cancer-related genes in 102 lesions. There were significant differences in the clinicopathological and molecular variables between small intestinal-and gastric-type tumors, which suggests the presence of at least two separate carcinogenic pathways in non-ampullary duodenal adenocarcinomas. The prevalence of CIMP-positive lesions was higher in intramucosal adenocarcinomas than in adenomas. Thus, concurrent hypermethylation of multiple CpG islands is likely associated with development of non-ampullary duodenal intramucosal adenocarcinomas. Mutation analysis showed that APC was the most frequently mutated gene in these lesions (56/102; 55%), followed by KRAS (13/102; 13%), LRP1B (10/102; 10%), GNAS (8/102; 8%), ERBB3 (7/102; 7%), and RNF43 (6/102; 6%). Additionally, the high prevalence of diffuse or focal nuclear β-catenin accumulation (87/102; 85%) as well as mutations of WNT pathway components (60/102; 59%) indicates the importance of WNT signaling to the initiation of duodenal adenomas. The higher than previously reported frequency of APC gene mutations in small bowel adenocarcinomas as well as the difference in the APC mutation distributions between small intestinal-type adenomas and intramucosal adenocarcinomas may indicate that the adenoma-carcinoma sequence has only limited involvement in duodenal carcinogenesis.

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Molecular characterization of sessile serrated adenoma/polyps with dysplasia/carcinoma based on immunohistochemistry, next-generation sequencing, and microsatellite instability testing: a case series study

Cited by 30 publications

References 48 publications

Clinicopathological features, diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Clinicopathological features, diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

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

Integrated genetic and epigenetic analysis of cancer‐related genes in non‐ampullary duodenal adenomas and intramucosal adenocarcinomas

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