scholarly journals NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions

2021 ◽  
Author(s):  
Jung Ho Kim ◽  
Jeong Hoon Hong ◽  
Yoon‐La Choi ◽  
Ji Ae Lee ◽  
Mi‐kyoung Seo ◽  
...  
Keyword(s):  
Serrated Lesions ◽  
Serrated Neoplasia Pathway

scholarly journals Curriculum review: serrated lesions of the colorectum

2019 ◽  
Vol 11 (3) ◽  
pp. 243-248
Author(s):  
Angad Singh Dhillon ◽  
Hajir Ibraheim ◽  
Susi Green ◽  
Noriko Suzuki ◽  
Siwan Thomas-Gibson ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Cumulative Effect ◽  
Low Grade ◽  
Epigenetic Alterations ◽  
Curriculum Review ◽  
Normal Colonic Epithelium ◽  
Surveillance Interval ◽  
Serrated Lesions ◽  
The Uk ◽  
Serrated Neoplasia Pathway

Colorectal cancer (CRC) is the second leading cause of death from cancer in the UK. Sporadic CRC evolves by the cumulative effect of genetic and epigenetic alterations. Typically, over the course of several years, this leads to the transformation of normal colonic epithelium to benign adenomatous polyp, low-grade to high-grade dysplasia and finally cancer—the adenoma-carcinoma sequence. Over the last decade, the serrated neoplasia pathway which progresses by methylation of tumour suppressing genes has been increasingly recognised as an important alternative pathway accounting for up to 30% of CRC cases. Endoscopists should be aware of the unique features of serrated lesions so that their early detection, appropriate resection and surveillance interval can be optimised.

scholarly journals Immune environment in serrated lesions of the colon: intraepithelial lymphocyte density, PD-1, and PD-L1 expression correlate with serrated neoplasia pathway progression

2019 ◽  
Vol 83 ◽  
pp. 115-123 ◽  
Author(s):  
Gabriel Acosta-Gonzalez ◽  
Madhu Ouseph ◽  
Kara Lombardo ◽  
Shaolei Lu ◽  
Jonathan Glickman ◽  
...  
Keyword(s):  
Intraepithelial Lymphocyte ◽  
Serrated Lesions ◽  
Serrated Neoplasia Pathway

scholarly journals NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions

2021 ◽  
Author(s):  
Jung Ho Kim ◽  
Jeong Hoon Hong ◽  
Yoon-La Choi ◽  
Ji Ae Lee ◽  
Mi-kyoung Seo ◽  
...  
Keyword(s):  
Drug Targets ◽  
Cpg Island ◽  
Colorectal Carcinogenesis ◽  
Wild Type ◽  
Cpg Island Methylator Phenotype ◽  
Braf Mutations ◽  
Epithelial Tumor ◽  
Age Related ◽  
Serrated Lesions ◽  
Serrated Neoplasia Pathway

Background: NTRK fusions are emerging tissue-agnostic drug targets in malignancies including colorectal cancers (CRCs), but their detailed landscape in the context of various colorectal carcinogenesis pathways remains to be investigated. Methods: Pan-TRK expression was assessed by immunohistochemistry in retrospectively collected colorectal epithelial tumor tissues, including 441 CRCs (133 microsatellite instability-high (MSI-high) and 308 microsatellite stable (MSS)) and 565 premalignant colorectal lesions (300 serrated lesions and 265 conventional adenomas). TRK-positive cases were subjected to next-generation sequencing and/or fluorescence in situ hybridization to confirm NTRK rearrangements. Results: TRK positivity was not observed in any of the MSS CRCs, conventional adenomas, traditional serrated adenomas, or hyperplastic polyps, whereas TRK positivity was observed in 11 of 58 (19%) sporadic MSI-high CRCs, 4 of 23 (17%) sessile serrated lesions with dysplasia (SSLDs), and 5 of 132 (4%) SSLs. The 11 TRK-positive MSI-high CRCs commonly harbored CpG island methylator phenotype-high (CIMP-high), MLH1 methylation, KRAS/BRAF wild-type, and NTRK1 or NTRK3 fusion (TPM3-NTRK1, TPR-NTRK1, LMNA-NTRK1, SFPQ-NTRK1, ETV6-NTRK3, or EML4-NTRK3). Both NTRK1 or NTRK3 rearrangement and KRAS/BRAF wild-type were detected in all nine TRK-positive SSL(D)s, seven of which demonstrated MSS and/or CIMP-low. TRK overexpression and early dysplastic changes are occasionally co-localized in the crypt base area of SSLs. Age-related occurrence patterns suggest that the progression interval from NTRK-rearranged SSLs to CRCs may be shorter than from BRAF-mutated SSLs to CRCs. Conclusion: NTRK-rearranged colorectal tumors develop exclusively through the serrated neoplasia pathway and can be initiated from non-dysplastic SSLs without KRAS/BRAF mutations prior to full occurrence of MSI-high/CIMP-high.

Correlation of Metabolic Risk Factors with Sessile Serrated Lesions

2020 ◽  
Vol 29 (2) ◽  
pp. 175-179
Author(s):  
Melania Macarie ◽  
Simona Bataga ◽  
Simona Mocan ◽  
Monica Pantea ◽  
Razvan Opaschi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Statistical Significance ◽  
Interval Cancer ◽  
Metabolic Risk Factors ◽  
Control Group ◽  
Anatomical Site ◽  
Metabolic Risk ◽  
Right Colon ◽  
Serrated Lesions ◽  
The Right

Background and Aims: The importance of sessile serrated lesions (SSLs) in the pathogenesis of colorectal carcinoma has been recently established. These are supposed to cause the so-called “interval cancer”, having a rapidly progressive growth and being difficult to detect and to obtain an endoscopic complete resection. We aimed to establish the most important metabolic risk factors for sessile serrated lesions. Methods: We performed a retrospective case-control study, on a series of 2918 consecutive patients who underwent colonoscopy in Gastroenterology and Endoscopy Unit, County Clinical Emergency Hospital, Târgu-Mureș, Romania between 1 st of January 2015-31 th of December 2017. In order to evaluate the metabolic risk factors for polyps’ development, enrolled participants were stratified in two groups, a study group, 33 patients with SSLs lesions, and a control group, 138 patients with adenomatous polyps, selected by systematic sampling for age and anatomical site. Independent variables investigated were: gender, smoking, alcohol consumption, obesity, arterial hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, nonalcoholic liver disease. Results: For SSLs the most common encountered localization was the right colon in 30.55% of cases. By comparative bivariate analysis between SSLs group and control group, it was observed that hypertension (p=0.03, OR 2.33, 95 %CI 1.03-5.24), obesity (p=0.03, OR 2.61, 95 %CI 1.08-6.30), hyperuricemia (p=0.04, OR 2.72, 95 %CI 1.28-7.55), high cholesterol (p=0.002, OR 3.42; 95 %CI 1.48-7.87), and high triglycerides level (p=0.0006, OR 5.75; 95 %CI 1.92-17.2) were statistically associated with SSLs development. By multivariate analysis hypertension and hypertriglyceridemia retained statistical significance. Conclusions: Our study showed that the highest prevalence of SSLs was in the right colon and hypertension and increased triglycerides levels were associated with the risk of SSLs development. These risk factors are easy to detect in clinical practice and may help identifying groups with high risk for colorectal cancer, where screening is recommended.

scholarly journals Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1087-1095
Author(s):  
Michele Sacco ◽  
Fatima Domenica Elisa De Palma ◽  
Elia Guadagno ◽  
Mariano Cesare Giglio ◽  
Roberto Peltrini ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Detection Rate ◽  
Epidemiological Data ◽  
Screening Colonoscopy ◽  
Current Evidence ◽  
Surveillance Program ◽  
Cancer Risk Factors ◽  
Serrated Polyps ◽  
Serrated Lesions ◽  
Molecular Aspects

AbstractIn 2010, serrated polyps (SP) of the colon have been included in the WHO classification of digestive tumors. Since then a large corpus of evidence focusing on these lesions are available in the literature. This review aims to analyze the present data on the epidemiological and molecular aspects of SP. Hyperplastic polyps (HPs) are the most common subtype of SP (70–90%), with a minimal or null risk of malignant transformation, contrarily to sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs), which represent 10–20% and 1% of adenomas, respectively. The malignant transformation, when occurs, is supported by a specific genetic pathway, known as the serrated-neoplasia pathway. The time needed for malignant transformation is not known, but it may occur rapidly in some lesions. Current evidence suggests that a detection rate of SP ≥15% should be expected in a population undergoing screening colonoscopy. There are no differences between primary colonoscopies and those carried out after positive occult fecal blood tests, as this screening test fails to identify SP, which rarely bleed. Genetic similarities between SP and interval cancers suggest that these cancers could arise from missed SP. Hence, the detection rate of serrated-lesions should be evaluated as a quality indicator of colonoscopy. There is a lack of high-quality longitudinal studies analyzing the long-term risk of developing colorectal cancer (CRC), as well as the cancer risk factors and molecular tissue biomarkers. Further studies are needed to define an evidence-based surveillance program after the removal of SP, which is currently suggested based on experts’ opinions.

scholarly journals Effects of Somatic Methylation in Colonic Polyps on Risk of Developing Metachronous Advanced Colorectal Lesions

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 246
Author(s):  
Oscar Murcia ◽  
Alejandro Martínez-Roca ◽  
Miriam Juárez ◽  
Mar Giner-Calabuig ◽  
Miren Alustiza ◽  
...  
Keyword(s):  
Cpg Island ◽  
Risk Estimation ◽  
Colonic Polyps ◽  
Cpg Island Methylator Phenotype ◽  
Polyp Size ◽  
Serrated Lesions ◽  
Amplification Technique ◽  
Methylator Phenotype ◽  
The Relationship ◽  
Dependent Probe

The utility of molecular markers for predicting the risk of metachronous advanced colorectal lesions (MACLs) remains poorly investigated. We examined the relationship between somatic hypermethylation in polyps at baseline and the risk of developing MACL. This retrospective cohort study included 281 consecutive patients with colonic polyps who were enrolled between 2007 and 2009 and followed-up until 2014. MACLs were defined as adenomas of >10 mm, high-grade dysplasia, or with a villous component; and serrated lesions of >10 mm or with dysplasia. In total, 595 polyps were removed at baseline colonoscopy and analyzed for pathological characteristics and CpG island methylator phenotype (CIMP) using the MS-MLPA (Methylation-Specific -- Multiplex Ligation-dependent Probe Amplification) technique. Forty-five patients (16.0%) showed at least one CIMP+ polyp. MACL risk was higher in patients with CIMP+ polyps (odds ratio (OR), 4.50; 95% CI, 1.78–11.4; p = 0.002). Patients with CIMP+ polyps also exhibited shorter time to MACL development (33.8 months vs. 50.1 months; p < 0.001), even with adjustment for polyp size and number (OR, 2.40; 95% CI, 1.33–4.34). Adding CIMP analysis improved the sensitivity (57.0% to 70.9%), negative predictive value (71.1% to 77.3%), and overall accuracy (49.8% to 52.0%) for MACL risk estimation. These results highlight that CIMP may be a useful marker for endoscopic surveillance.

scholarly journals Morphological Characteristics, Classifications and Difficulties in the Use of Diagnostic Criteria for Serrated Lesions of the Large Intestine

2021 ◽  
Author(s):  
Cesar de Souza Bastos Junior ◽  
Vera Lucia Nunes Pannain ◽  
Adriana Caroli-Bottino
Keyword(s):  
Diagnostic Criteria ◽  
Morphological Characteristics ◽  
World Health ◽  
Diagnostic Tools ◽  
Serrated Adenoma ◽  
The Past ◽  
The World ◽  
Serrated Lesions ◽  
Health Organization

Abstract Introduction Colorectal carcinoma (CRC) is the most common gastrointestinal neoplasm in the world, accounting for 15% of cancer-related deaths. This condition is related to different molecular pathways, among them the recently described serrated pathway, whose characteristic entities, serrated lesions, have undergone important changes in their names and diagnostic criteria in the past thirty years. The multiplicity of denominations and criteria over the last years may be responsible for the low interobserver concordance (IOC) described in the literature. Objectives The present study aims to describe the evolution in classification of serrated lesions, based on the last three publications of the World Health Organization (WHO) and the reproducibility of these criteria by pathologists, based on the evaluation of the IOC. Methods A search was conducted in the PubMed, ResearchGate and Portal Capes databases, with the following terms: sessile serrated lesion; serrated lesions; serrated adenoma; interobserver concordance; and reproducibility. Articles published since 1990 were researched. Results and Discussion The classification of serrated lesions in the past thirty years showed different denominations and diagnostic criteria. The reproducibility and IOC of these criteria in the literature, based on the kappa coefficient, varied in most studies, from very poor to moderate. Conclusions Interobserver concordance and the reproducibility of microscopic criteria may represent a limitation for the diagnosis and appropriate management of these lesions. It is necessary to investigate diagnostic tools to improve the performance of the pathologist's evaluation, for better concordance, and, consequently, adequate diagnosis and treatment.

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