Colorectal carcinoma occurring via the adenoma–carcinoma pathway in patients with serrated polyposis syndrome

Nakamura, Fumiya; Sato, Yasushi; Okamoto, Koichi; Fujino, Yuichi; Mitsui, Yasuhiro; Kagemoto, Kaizo; Kawaguchi, Tomoyuki; Miyamoto, Hiroshi; Muguruma, Naoki; Sonoda, Tomoko; Tsuneyama, Koichi; Takayama, Tetsuji

doi:10.1007/s00535-022-01858-8

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…Several groups, including the US Multisociety Task Force and European Society of Gastrointestinal Endoscopy, have proposed an appropriate surveillance interval after the resection of serrated polyps in published guidelines [ 115 – 117 ]. Since TSAs, large SSLs (≥ 10 mm), and SSLDs yield metachronous advanced neoplasia or CRC risks similar to conventional adenomas [ 118 ], these guidelines recommend 3-year intervals after polypectomy of these polyps. However, considering that SSLDs have high rates of incompletely excised lesions and rapid growth to invasive carcinoma, the surveillance interval after removal of SSLDs may need to be shorter.…”

Section: Differences In Therapeutic Indications Between Ssls and Ssldsmentioning

confidence: 99%

Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

et al. 2023

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The serrated neoplasia pathway constitutes an “alternative route” to colorectal cancer (CRC), and sessile serrated lesions with dysplasia (SSLDs) are an intermediate step between sessile serrated lesions (SSLs) and invasive CRC in this pathway. While SSLs show indolent growth before becoming dysplastic (> 10–15 years), SSLDs are considered to rapidly progress to either immunogenic microsatellite instable-high (MSI-H) CRC (presumably 75% of cases) or mesenchymal microsatellite stable (MSS) CRC. Their flat shapes and the relatively short window of this intermediate state make it difficult to detect and diagnose SSLDs; thus, these lesions are potent precursors of post-colonoscopy/interval cancers. Confusing terminology and the lack of longitudinal observation data of serrated polyps have hampered the accumulation of knowledge about SSLDs; however, a growing body of evidence has started to clarify their characteristics and biology. Together with recent efforts to incorporate terminology, histological studies of SSLDs have identified distinct dysplastic patterns and revealed alterations in the tumor microenvironment (TME). Molecular studies at the single-cell level have identified distinct gene alterations in both the epithelium and the TME. Mouse serrated tumor models have demonstrated the importance of TME in disease progression. Advances in colonoscopy provide clues to distinguish pre-malignant from non-malignant-SSLs. Recent progress in all aspects of the field has enhanced our understanding of the biology of SSLDs. The aim of this review article was to assess the current knowledge of SSLDs and highlight their clinical implications.

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Section: Differences In Therapeutic Indications Between Ssls and Ssldsmentioning

confidence: 99%

Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

et al. 2023

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“…The proportion we found was in line with a meta-analysis including 4 SPS cohorts (49%) ( 26 ). Another recent study reported a lower proportion of BRAF V600E -CRCs (27.8%) ( 18 ); however, this regarded a cohort in Japan where a lower incidence of BRAF V600E -CRC in the general population has been described ( 27 ). In addition, the authors applied different outcome definitions to classify sCRCs, thus limiting further comparison.…”

Section: Discussionmentioning

confidence: 93%

“…In fact, co-occurrence of conventional adenomas in individuals with SPS might lead to a higher CRC risk, as previously suggested ( 16 , 17 ). In a recent study, 11/19 CRCs (58%) detected in patients with SPS were suggested to be derived from conventional adenomas, as indicated by an adjacent conventional adenoma or the presence of an APC / CTNNB1 mutation and a TP53 mutation ( 18 ). Also other studies observed the presence of a BRAF V600E in 46%–53% of the CRCs in patients with SPS, suggesting that a proportion of CRCs may not originate from serrated polyps ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

Polyps and colorectal cancer in serrated polyposis syndrome: contribution of the classical adenoma-carcinoma and serrated neoplasia pathways

Toledo

IJspeert

Boersma

et al. 2023

Clin Transl Gastroenterol

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INTRODUCTION: Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS. METHODS: We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAF V600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAF V600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAF V600E mutation status. RESULTS: Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAF V600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAF V600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAF wt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAF V600E -CRCs (1 vs 14). DISCUSSION: Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.

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“…APC mutation in the intestine played an essential role in the progression of CRA [ 21 ]. Wnt/β-catenin is closely related to stemness and promotes tumor proliferation via regulation of stem genes [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma

et al. 2023

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Background Colorectal cancer (CRC), ranking third in cancer prevalence and second in mortality worldwide, is mainly derived from colorectal adenoma (CRA). CRA is a common benign disease in the intestine with rapidly increasing incidence and malignant potential. Therefore, this study aimed to recognize significant biomarkers and original pathogenesis in CRA. Methods Transcriptome data of GSE8671, GSE37364, and GSE15960 were downloaded from the Gene Expression Omnibus (GEO) datasets, and differentially expressed genes (DEGs) were screened. Functional pathways enrichment, protein–protein interaction (PPI) network, stem-correlation analysis, CIBERSORT, risk score and survival analyses were performed. RT-qPCR and immunohistochemical staining were applied to verify our results. Results Screening for significant DEGs in each dataset, we identified 230 robust DEGs, including 127 upregulated and 103 downregulated genes. Functional pathways enrichment showed that these DEGs were distinctly enriched in various tumor-associated pathways, such as growth factor activity, extracellular structure organization, neutrophil activation, and inflammatory response. We filtered out two hub genes via STRING and Modules analysis, including CA2 and HSD11B2. Stem-correlation analysis displayed that hub genes were negatively associated with stem-related genes (Olfm4, CD44, CCND1 and MYC). The CIBERSORT algorithm indicated that Macrophage2, activated mast cells, and Neutrophils promoted CRA progression through inflammation. Survival analysis showed that CA2 and HSD11B2 were positively associated with survival outcomes in CRC. Conclusion Our study has successfully identified the critical role of two core genes in the development and oncogenesis of CRA, which provides novel insight into the underlying pathogenesis, potential biomarkers and therapeutic targets.

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Colorectal carcinoma occurring via the adenoma–carcinoma pathway in patients with serrated polyposis syndrome

Cited by 10 publications

References 40 publications

Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

Polyps and colorectal cancer in serrated polyposis syndrome: contribution of the classical adenoma-carcinoma and serrated neoplasia pathways

Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma

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