Association of Large Serrated Polyps With Synchronous Advanced Colorectal Neoplasia

Department of Medicine, University of California, San Francisco, 94115, USA.
The American Journal of Gastroenterology (Impact Factor: 10.76). 02/2009; 104(3):695-702. DOI: 10.1038/ajg.2008.166
Source: PubMed


Serrated polyps of the colorectum are a histologically and genetically heterogeneous group of lesions, which include classic hyperplasic polyps, sessile serrated adenomas (SSAs), and traditional serrated adenomas. Accumulating evidence suggests that they may have different malignancy potentials. This study sought to determine the association between the presence of large serrated colorectal polyps and synchronous advanced colorectal neoplasia.
Among 4,714 asymptomatic subjects who underwent screening colonoscopy, cases of advanced colorectal neoplasia (tubular adenoma > or =1 cm, adenoma with any villous histology, adenoma with carcinoma in situ / high-grade dysplasia, or invasive adenocarcinoma) were compared with controls without advanced neoplasia with respect to candidate predictors, including age, sex, family history of colorectal cancer, body mass index, the presence and number of small tubular adenomas (<1 cm), the presence of multiple small serrated polyps (<1 cm), and the presence of large serrated polyps (> or =1 cm). Independent predictors of advanced neoplasia were determined by multivariate logistic regression analysis.
Among 467 cases and 4,247 controls, independent predictors of advanced colorectal neoplasia were increasing age (odds ratio (OR)=4.51; 95% confidence interval (CI), 1.43-14.3; P=0.01 for subjects > or =80 years vs. 50-54 years of age); non-advanced tubular adenomas (OR=2.33; 95% CI 1.37-3.96, P=0.0017 for 3 or more); and large serrated polyps (OR=3.24; 95% CI 2.05-5.13, P<0.0001). In total, 109 subjects (2.3% of the study population) had large serrated polyps. Right- and left-sided large serrated polyps had a similar association with advanced colorectal neoplasia (OR=3.38 vs. 2.66, P=0.62).
Large serrated polyps are strongly and independently associated with synchronous advanced colorectal neoplasia. Our results suggest that large serrated polyps may be a marker for advanced colorectal neoplasia. Further studies are needed to determine whether the association with advanced neoplasia differs among subsets of serrated polyps, particularly SSAs and classic hyperplastic polyps.

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    • "The time interval of the collected CSP was also often less than a year. Moreover, some of them did not specify the subtypes of CSP or only included SSA [16] [18] [27]. Furthermore, TSA has often been omitted or included in the CSP group, and is less characterized. "
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    ABSTRACT: Sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) are considered as precursors of colorectal cancer, and are often diagnostic challenges. Their true prevalence is masked by significant inter-observer variations. To investigate the true prevalence and synchronous colorectal carcinoma (sCRC) of colorectal serrated polyps (CSP) and their associated factors, we first retrospectively identified all colorectal polyps collected at our institution between June 1995 and May 2013. After centrally reclassifying all CSP to reduce inter-observer variations, Chi-square tests and logistic regression analyses were used to analyze the potential factors. Among the included 5501 colorectal polyps, 499 CSP of 428 patients were identified and studied, including 353 hyperplastic polyps (HP, 70.7%), 80 SSA (16.0%), 61 TSA (12.2%) and 5 mixed polyp (1.0%). Diagnostic disagreements were found in 68 CSP (13.63% of CSP). SSA and TSA were more often larger than 5 mm and in proximal colon than HP. SSA were also more likely associated with older age (p=0.005), size ≥5 mm (p<0.001) and ≥3 polyps (p=0.004) than HP in distal colon, but only more likely associated with older age (p=0.006) in proximal colon. Multivariate regression analysis demonstrated that CSP with sCRC, compared with CSP without sCRC, were linked to CSP size ≥1 cm (vs <1 cm, odds ratio [OR] 4.412, 95% confidence interval [CI] 1.684-11.556, P=0.003) and a diagnosis of SSA or TSA (vs HP, OR 6.194, 95% CI 1.870-20.513, P=0.003 and OR 6.754, 95% CI 1.981-23.028, P=0.002, respectively), but not age, gender, polyp number and polyp shape. SSA and TSA are similarly often associated with sCRC (P=0.460). In conclusion, histology subtypes and polyp size may serve as markers for sCRC of CSP. SSA and TSA may warrant careful endoscopic examinations and similar follow-up intervals.
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    ABSTRACT: Der serratierte Karzinogeneseweg im Kolorektum ist in Bezug auf die präinvasiven Vorstufen, die molekularen Pfade und die Prognose der Karzinome heterogen: Bei den serratierten Adenokarzinomen lassen sich ein „Low-risk-Subtyp“ [Häufigkeit <20%, mit meist proximaler Lokalisation, dem sessilen serratierten Adenom (SSA) als Vorläuferläsion, BRAF-Mutation, MSI-H, CpG-Methylierung/hMLH1-Ausfall und einer Fünfjahresüberlebensrate von >70%] sowie ein „High-risk-Subtyp“ [Häufigkeit >80%, mit meist distaler Lokalisation, dem traditionellen serratierten Adenom (TSA) als Vorläuferläsion, KRAS-Mutation, MSI-L/MSS, CpG-Methylierung/p53 und einer Fünfjahresüberlebensrate von <30%] unterscheiden. Eine molekularpathologische Bestimmung des Mikrosatellitenstatus und einer BRAF- oder KRAS-Mutation in Verbindung mit einer hMLH1- und p53-Immunhistochemie lässt eine Unterscheidung dieser beiden Typen zu und wird klinisch zunehmend relevant. The serrated pathway of colorectal carcinogenesis is heterogeneous with respect to its precursor lesions, molecular alterations and its prognosis. The low-risk-subtype of serrated adenocarcinomas is less frequent (<20% of all serrated adenocarcinomas) and characterized by proximal location, BRAF-mutation, high CpG-island methylation with loss of MLH1-expression and MSI-H phenotype. The assumed precursor lesion of this subtype is the sessile serrated adenoma and the 5-year overall survival is >70%. The high-risk-subtype is more frequent (>80% of all serrated adenocarcinomas) and characterized by distal location, KRAS mutation, MSI-L/MSS phenotype, lower CpG-island methylation, possible p53 accumulation; the assumed precursor lesion is the traditional serrated adenoma and the prognosis is unfavorable (<30% 5-year overall survival). The analysis of MSI status, KRAS and BRAF mutational status and immunohistochemical analyses of hMLH1 and p53 expression enables the distinction between these two subtypes and is therefore clinically relevant, especially since treatment options for the two subtypes may differ in the future. SchlüsselwörterSessiles serratiertes Adenom-Traditionelles serratiertes Adenom-Serratiertes Adenokarzinom-Serratierter Karzinogeneseweg-Kolorektum KeywordsSessile serrated adenoma-Traditional serrated adenoma-Serrated adenocarcinoma-Serrated carcinogenesis pathway-Colorectum
    Der Pathologe 02/2009; 31(1):9-15. DOI:10.1007/s00292-009-1239-8 · 0.39 Impact Factor
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    ABSTRACT: The serrated neoplastic pathway describes a molecular and morphologic continuum, whereby a subset of architecturally serrated polyps progress to colorectal cancers that show BRAF mutation and widespread gene promoter hypermethylation. A subtype of hyper plastic polyp called sessile serrated adenoma has been firmly placed as the dominant precursor lesion in this pathway, whereas the role of the serrated adenoma in this or an alternate serrated pathway requires clarification. The existence of at least one serrated pathway to colorectal carcinogenesis is well established, and research efforts are focused on better defining serrated polyp subtypes macroscopically, histologically, and at the molecular level to ensure optimal clinical management.
    Current Colorectal Cancer Reports 04/2009; 5(2):75-83. DOI:10.1007/s11888-009-0012-y
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