Clinicopathological factors associated with <scp>BRAF</scp>‐V600E mutation in colorectal serrated adenomas

Travaglino, Antonio; D’Armiento, Francesco Paolo; Cassese, Gianluca; Campanino, Maria Raffaela; Borrelli, Giorgio; Pignatiello, Sara; Luglio, Gaetano; Maione, Francesco; Palma, Giovanni Domenico De; D’Armiento, Maria

doi:10.1111/his.13846

Cited by 8 publications

(11 citation statements)

References 64 publications

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“…The role of MUC6 was evaluated in SSA/Ps lesions and is controversial [84]. Nevertheless, MUC6 was assessed to be a supportive immunohistochemical marker to differentiate SSA/Ps from TSAs [97,98].…”

Section: Molecular Features Of the Serrated Colorectal Precursor Lmentioning

confidence: 99%

“…The clinical role of MSI and CIMP has not been precisely described as opposed to BRAF and KRAS mutations. In general, BRAF mutated, MSI and CIMP CRCs are more frequent in females and often localized in the proximal colon [98,161]. MSI CRCs present a good prognosis, while BRAF mutated and CIMP tumors are related to a later age-of-onset and to a poor clinical outcome [38,65].…”

Section: Clinical Relevance Of Molecular Alterations In the Serratmentioning

confidence: 99%

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The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

Palma

D’Argenio

Pol

et al. 2019

Cancers

146

102

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Colorectal cancer (CRC) is a leading cause of cancer death worldwide. It includes different subtypes that differ in their clinical and prognostic features. In the past decade, in addition to the conventional adenoma-carcinoma model, an alternative multistep mechanism of carcinogenesis, namely the “serrated pathway”, has been described. Approximately, 15 to 30% of all CRCs arise from neoplastic serrated polyps, a heterogeneous group of lesions that are histologically classified into three morphologic categories: hyperplastic polyps, sessile serrated adenomas/polyps, and the traditional serrated adenomas/polyps. Serrated polyps are characterized by genetic (BRAF or KRAS mutations) and epigenetic (CpG island methylator phenotype (CIMP)) alterations that cooperate to initiate and drive malignant transformation from normal colon mucosa to polyps, and then to CRC. The high heterogeneity of the serrated lesions renders their diagnostic and pathological interpretation difficult. Hence, novel genetic and epigenetic biomarkers are required for better classification and management of CRCs. To date, several molecular alterations have been associated with the serrated polyp-CRC sequence. In addition, the gut microbiota is emerging as a contributor to/modulator of the serrated pathway. This review summarizes the state of the art of the genetic, epigenetic and microbiota signatures associated with serrated CRCs, together with their clinical implications.

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Section: Molecular Features Of the Serrated Colorectal Precursor Lmentioning

confidence: 99%

Section: Clinical Relevance Of Molecular Alterations In the Serratmentioning

confidence: 99%

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

Palma

D’Argenio

Pol

et al. 2019

Cancers

146

102

View full text Add to dashboard Cite

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“…20,25 BRAF mutations appear to be particularly common in proximal TSAs < 10 mm in size. 21 This genetic profile is the same as that of microvesicular HPs and SSLs, suggesting that proximally located TSAs may develop from one of these precursor lesions. A third, smaller group of TSAs have been identified that harbour neither BRAF nor KRAS mutations.…”

Section: G O B L E T C E L L -R I C H H P S a N D T S A Smentioning

confidence: 68%

“…20 Microvesicular HPs and left-sided SSLs show only low-level to intermediatelevel genomic methylation, whereas right-sided SSLs show high-level methylation. 20,21 CRC developing along this pathway also shows BRAF V600E mutation, and this is associated with high-level genomic methylation [CpG island methylator phenotype (CIMP)-high status], resulting in inactivation of certain genes. In particular, methylation of the promoter sequence for MLH1 leads to inactivation of this gene and therefore to loss of expression of MLH1 (and its partner molecule PMS2) and microsatellite instability (MSI) in areas of dysplasia (dysplasia NOS and minimal deviation dysplasia) arising in SSLs and associated CRCs.…”

Section: I C R O V E S I C U L a R H P S A N D S S L Smentioning

confidence: 99%

The spectrum of serrated colorectal lesions—new entities and unanswered questions

Bateman

2021

Histopathology

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The spectrum of serrated colorectal lesions-new entities and unanswered questions Hyperplastic polyps (HPs) of the colon and rectum were historically thought not to be associated with an increased risk of development of colorectal cancer (CRC). The recognition of variants of serrated colorectal lesions that possessed relatively subtle but significant morphological differences from those of HPs and that could be associated with epithelial dysplasia and CRC led to the characterisation of sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). These links were supported by the identification of genetic alterations that are commonly found in HPs, SSLs, TSAs, and CRC, e.g. BRAF and KRAS mutations. The 'serrated pathway' to CRC may progress faster than the traditional 'adenoma-carcinoma sequence', underlining the importance of identifying these lesions. The diagnostic histological criteria for SSLs have since been more clearly defined, in parallel with a drive to increase the recognition of these lesions at endoscopy. The existence of lesions showing overlapping morphological and molecular features with those of HPs, SSLs and TSAs has most recently been highlighted-including mucin-rich TSA, serrated tubulovillous adenoma, and those showing mixed histological features, e.g. comprising differing combinations of HP, SSL, and TSA. Morphological and molecular studies of this range of lesions are providing insights into the relationships of serrated colorectal lesions with each other and with CRC. This article provides an overview of the current understanding of serrated colorectal lesions, including a discussion of those with overlapping and mixed features.

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“…Sessile serrated adenomas have a higher risk of developing into malignant tumors because of their special biologic behavior, so they should be paid more attention. 8,9…”

Section: Risk Factors For Early and Late Adenoma Recurrence With Regamentioning

confidence: 99%

Risk factors for early and late adenoma recurrence with regard to the histological margin

Zhu

2019

Gastrointestinal Endoscopy

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no severe or serious adverse events or deaths were registered. Given the observational nature of our study, assessment of blood electrolyte or creatinine was not feasible. Nevertheless, no clinical event attributable to electrolyte imbalance or dehydration was observed in any patient, confirming good safety of NER1006 in a real-life setting. Regarding concerns about the use of NER1006 in the elderly, 45% of the patients in our cohort were >65 years old, and among those the median age was 73.6 AE 6.1 years (range, 65-89 years), confirming the validity of these data also in the elderly population. On the basis of this evidence, we believe that at present no alert can be raised regarding the safety profile of NER1006 and that this product can be administered to most patients without specific limitations.

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

Cited by 8 publications

References 64 publications

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

The spectrum of serrated colorectal lesions—new entities and unanswered questions

Risk factors for early and late adenoma recurrence with regard to the histological margin

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