Clinicopathologic and Molecular Characteristics of Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma

Okamura, Takuma; Hashimoto, Taiki; Naka, Tomoaki; Yoshida, Teruhiko; Tanabe, Noriko; Ogawa, Reiko; Yamada, Masayoshi; Saito, Yutaka; Yatabe, Yasushi; Sekine, Shigeki

doi:10.1097/pas.0000000000001502

Cited by 4 publications

(5 citation statements)

References 42 publications

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“…Sporadic and FAP-associated TSAs follow the serrated neoplasia pathway, associated with KRAS and BRAF mutations in most instances 13. All tested TSAs from both groups in our study were BRAF wild-type.…”

Section: Discussionmentioning

confidence: 52%

“…Sporadic and FAP-associated TSAs follow the serrated neoplasia pathway, associated with KRAS and BRAF mutations in most instances. 13 All tested TSAs from both groups in our study were BRAF wild-type. KRAS mutations in exon 2 and 3 were not detected in FAP-associated TSAs (0/5 and 0/10 TSAs, respectively) but were identified in a minority of nonsyndromic TSAs (3/9 and 0/9 TSAs, respectively).…”

Section: Discussionmentioning

confidence: 88%

“…Previous studies described the occurrence of colonic FAP-associated TSAs and found that tumorigenesis follows the serrated neoplasia pathway. 13,14 In this study, we describe the clinicopathologic and molecular features of small bowel FAP-associated TSAs and compare their characteristics with those of sporadic TSAs.…”

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confidence: 99%

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Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma of the Small Intestine

Alruwaii

Chianchiano²,

Larman³

et al. 2021

American Journal of Surgical Pathology

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Familial adenomatous polyposis (FAP) is an inherited cancer predisposition syndrome associated with numerous gastrointestinal tract adenomatous polyps, as well as gastric fundic gland polyps and pyloric gland adenomas in the upper gastrointestinal tract. While colonic FAP-associated traditional serrated adenomas (TSAs) have been reported in a few studies, small bowel FAP-associated adenomas with TSA morphology have not been characterized. This study describes the clinicopathologic and molecular findings of this type of adenoma in the small bowel of patients with FAP. We reviewed small bowel adenomas in 45 consecutive FAP patients to identify adenomas with zones showing slit-like serrations, cells with eosinophilic cytoplasm, ectopic crypt formation, and vesicular nuclei. Sporadic small bowel adenomas from 51 consecutive patients were also reviewed for adenomas with the same features. Of the 177 polyps from 45 FAP patients and 60 polyps from 51 nonsyndromic patients, 18 TSAs from 9 FAP patients (20%) and 10 TSAs from the sporadic group (19.6%) were identified. FAP patients presented at a younger age than nonsyndromic patients (median: 43 vs. 66; P=0.0048). FAP-associated TSAs were asymptomatic and smaller than sporadic TSAs (median size: 0.6 vs. 2.5 cm; P=0.00006). Immunostaining for β-catenin and testing for BRAF and KRAS mutations were performed in a subset of the cohort. Nuclear β-catenin was seen in 1 FAP-associated TSA and 3 nonsyndromic TSAs. All TSAs (FAP-associated and nonsyndromic) showed wild-type BRAF, while KRAS mutations were identified only in the nonsyndromic setting. In summary, small bowel FAP-associated and sporadic TSAs share a similar morphology, and the BRAF-serrated pathway does not contribute to their pathogenesis.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 88%

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Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma of the Small Intestine

Alruwaii

Chianchiano²,

Larman³

et al. 2021

American Journal of Surgical Pathology

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“…It is generally believed that Wnt pathway of SPs is mainly activated by a number of alternative mechanisms such as PTPRK-RSPO3 fusions and RNF43 mutations other than APC ( 28 , 34 ). Although recently, research is suggesting that APC mutations are likely the main pathogenic reason for WNT signaling activation in serrated pathway based on their high frequency ( 35 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

ERBB2 Mutations as Potential Predictors for Recurrence in Colorectal Serrated Polyps by Targeted Next-Generation Sequencing

Wang

Zhang

et al. 2022

Front. Oncol.

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BackgroundFollow-up guidelines for serrated polyps (SPs) are mainly based on factors such as histology and size with limited evidence. The underlying genomic mechanism of SPs in relation to recurrence risks is utterly unknown.MethodsWe applied targeted next-generation sequencing (NGS) approach on two groups of SPs [polyp-relapsed SPs (PRSPs) vs. polyp-free SPs (PFSPs)] based on the surveillance outcomes to compare differences of DNA variants in 71 colorectal cancer-associated genes. A multicenter validation cohort was established longitudinally from 2016 to 2019 to confirm the relevant results.ResultsAmong the 96 NGS samples, at least one mutant after filtration was detected in 90 samples (94%). Molecular profiling presented BRAF, KRAS, and APC as top 3 mutated genes. FBXW7, MSH2, and ERBB2 might be recurrence-relevant, while DMD, BRCA1, and BRCA2 might be negatively correlated with recurrence. Notably, ERBB2 mutants (R678Q and V842I) (n = 5) had higher risks of polyp recurrence than the wild types (n = 85), with a median polyp-free interval of 15 months compared to 26 months [P < 0.001; hazard ratio (HR) = 4.9; 95% confidence interval (CI) = 1.9–12.8]. Furthermore, a multicenter cohort composed by 321 SPs verified that ERBB2-mutated SPs had increased risks of polyp recurrence (P < 0.001; HR = 3.7; 95% CI = 2.3–6.0) and advanced neoplastic lesion (ANL) recurrence (P < 0.001; HR = 10.0; 95% CI = 2.7–36.9) compared with wild-type SPs, respectively.ConclusionsOur results are emphasizing that SP individuals with ERBB2 mutants are at higher risks of subsequent colorectal neoplasms. ERBB2 mutants might work as facilitated markers for prediction of high-risk SPs and might implicate a potential mechanism in the serrated pathway to colorectal carcinoma (CRC).

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“…The fourth report presented by Okamura et al clarified the molecular features of 37 TSAs from 21 FAP patients using next-generation sequencing and Sanger sequencing [ 6 ]. They showed KRAS and BRAF V600E mutations were observed in 18 (49%) and 14 (38%) FAP-associated TSAs, respectively, suggesting that the pathogenesis of FAP-associated TSAs is similar to that of sporadic TSAs.…”

Section: Discussionmentioning

confidence: 99%

Importance of sessile serrated lesions in a patient with familial adenomatous polyposis

Watanabe

Ishikawa

Ishiguro³

et al. 2021

Clin J Gastroenterol

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A 28-year-old male visited hospital because his mother had been diagnosed with familial adenomatous polyposis (FAP) with a pathological variant of the APC gene. Total colonoscopy showed that he has more than 100 polyps distributed throughout the colorectum, and the APC gene variant was also detected. After he was diagnosed with FAP, he received information that surgery was currently the only way to prevent the development of colorectal cancer. However, he firmly declined to undergo surgical procedures and decided to have strict follow-up with frequent endoscopic polypectomy to prevent the development of colorectal cancer. At the first endoscopy, polypectomy was performed on 52 polyps. Histological analysis of the dissected polyps showed that they were all adenomas, but adenocarcinoma was not detected. The second endoscopic polypectomy was performed after 4 months later. We found a pale 20 mm wide flat, elevated type polyp in the ascending colon with an adherent mucus cap that was resistant to washing off. After endoscopic mucosal resection, histological analysis revealed that there were two lesions in the polyps, a sessile serrated lesion (SSL) and SSL with dysplasia. SSL is a high-risk lesion for colorectal cancer, but it was reported to be rare in patients with FAP, and the existence of SSL suggested another carcinogenesis pathway in patients with FAP in addition to the adenoma-carcinoma sequence. Our report may be significant not only in consideration of the pathogenesis of FAP but also useful to raise awareness of SSL for clinicians who perform endoscopic polypectomy to prevent the development of colorectal cancer in patients with FAP.

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Clinicopathologic and Molecular Characteristics of Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma

Cited by 4 publications

References 42 publications

Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma of the Small Intestine

Familial Adenomatous Polyposis–associated Traditional Serrated Adenoma of the Small Intestine

ERBB2 Mutations as Potential Predictors for Recurrence in Colorectal Serrated Polyps by Targeted Next-Generation Sequencing

Importance of sessile serrated lesions in a patient with familial adenomatous polyposis

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