Qualities of sessile serrated adenoma/polyp/lesion and its borderline variant in the context of synchronous colorectal carcinoma

Mohammadi, Mahin; Kristensen, Michael Holmsgaard; Nielsen, Hans Jørgen; Bonde, Jesper; Holck, Susanne

doi:10.1136/jclinpath-2012-200803

Cited by 22 publications

(17 citation statements)

References 46 publications

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“…Here we showed that SSA/P/Ls and BSSA/P/Ls express CD133 significantly more often than do HPs. This observation corroborates our previous experience that several qualities of BSSA/P/Ls are more akin to SSA/P/Ls than to HPs 6 32. Specifically, we have demonstrated that the occurrence of BRAF mutation of BSSA/P/Ls did not differ from that of SSA/P/Ls and significantly exceeded that of HPs 32…”

Section: Discussionsupporting

confidence: 92%

“…In brief, we carried out a review of 8342 consecutive cases of colorectal polyps, coded as HP, whereby samples fulfilling criteria of SSA / P/L (a convincing presence of at least two of the following four structural abnormalities: dilatation of base of crypts, serration of base of crypts, branched crypts and horizontally oriented crypts) and BSSA/P/L (only one of the above structural alterations was convincingly present or at least two of these qualities were considered equivocally present) were identified. Based on surgical pathology files and patients’ records, cases with SCRC (27 SSA/P/Ls, 17 BSSA/P/Ls and 11 HPs) were identified 32. Polyp site was considered right-sided if located proximally to the hepatic flexure 33.…”

Section: Methodsmentioning

confidence: 99%

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The stem cell marker CD133 is highly expressed in sessile serrated adenoma and its borderline variant compared with hyperplastic polyp

et al. 2013

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Non-dysplastic serrated polyps (ND-SP) represent a heterogeneous group of colorectal lesions that comprise hyperplastic polyp (HP) and the non-dysplastic subset of sessile serrated adenoma/polyp/lesion (SSA/P/L) and its borderline variant (BSSA/P/L). Given the observer variation in their histological typing, the identification of reliable markers that assist in the characterisation is warranted. Most important is the identification of polyp qualities that may reflect the patients' risk of developing colorectal cancer. To address these issues, CD133 may represent a potential adjunct. Here we studied the discriminatory value of CD133 expression in the classification of ND-SPs and its distribution pattern in relation to synchronous colorectal carcinoma (SCRC). 39 SSA/P/Ls, 27 BSSA/P/Ls and 21 matched HPs were immunostained for CD133. The data were further correlated to the presence of SCRC and to polyp site and size. Ignoring SCRC status, CD133 was expressed more prominently in SSA/P/Ls than in HPs. The values for BSSA/P/Ls fell in between, yet closer to the SSA/P/L scorings. This observation was retained in the context of SCRC and for SSA/P/Ls not associated with SCRC. Right-sidedness and large size of the polyps more commonly associated with increased CD133 expression. CD133 expression was not a significant discriminator as to the SCRC status. BSSA/P/Ls are more closely aligned to SSA/P/L and further that SSA/P/L and BSSA/P/Ls fundamentally differ from HP by their CD133 immunoprofile, a notion that can be exploited in the diagnostic routine practice. Recorded data further indirectly support the idea that SSA/P/Ls are more prone to neoplastic progression than are HPs.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

The stem cell marker CD133 is highly expressed in sessile serrated adenoma and its borderline variant compared with hyperplastic polyp

et al. 2013

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“…13 On one hand, this has been interpreted as evidence that sessile serrated adenomas/polyps evolve from microvesicular hyperplastic polyps or on the other hand that microvesicular hyperplastic polyp features could belong to the morphologic spectrum of sessile serrated adenomas/polyps. 13 This implicates that there are borderline lesions 35 and therefore no clear line can be drawn between the morphology of microvesicular hyperplastic polyps and sessile serrated adenomas/polyps. It is likely that the progression between microvesicular hyperplastic polyp and sessile serrated adenoma/polyp is a continuum with BRAF V600E mutation as an early genetic event in the serrated neoplasia pathway.…”

Section: Discussionmentioning

confidence: 99%

Improved molecular classification of serrated lesions of the colon by immunohistochemical detection of BRAF V600E

et al. 2014

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BRAF V600E mutation in serrated lesions of the colon has been implicated as an important mutation and as a specific marker for the serrated carcinogenic pathway. Recent findings point to microvesicular hyperplastic polyps that have similar histologic and molecular features to sessile serrated adenomas/polyps, as potential colorectal carcinoma precursors. The aim of this study was to evaluate BRAF V600E mutation status by immunohistochemistry in serrated lesions of the colon with regard to histomorphology. We investigated 194 serrated lesions of the colon, comprising 42 sessile serrated adenomas/polyps, 16 traditional serrated adenomas, 136 hyperplastic polyps and 20 tubular/tubulovillous adenomas (conventional adenomas) with the novel BRAF V600E mutation-specific antibody VE1. In addition, BRAF exon 15 and KRAS exon 2 status was investigated by capillary sequencing in selected cases. All sessile serrated adenomas/polyps (42/42, 100%), 15/ 16 (94%) traditional serrated adenomas and 84/136 (62%) hyperplastic polyps were VE1 þ . None of the VE1 À serrated lesions showed BRAF V600E mutation. Forty out of 42 (95%) sessile serrated adenomas/polyps displayed areas with microvesicular hyperplastic polyp-like features. In microvesicular hyperplastic polyps, VE1 positivity was significantly associated with nuclear atypia (P ¼ 0.003); however, nuclear atypia was also present in VE1 À cases. Immunostaining with VE1 allows not only the detection of BRAF V600E mutation but also the correlation with histomorphology on a cellular level in serrated lesions. VE1 enables a subclassification of microvesicular hyperplastic polyps according to the mutation status. This improved classification of serrated lesions including immunohistochemical evaluation of BRAF V600E mutation may be the key to identify lesions with higher potential to progression into sessile serrated adenoma/polyp, and further to BRAF V600E-mutated colorectal cancer. Modern Pathology (2014) 27, 135-144; doi:10.1038/modpathol.2013; published online 26 July 2013Keywords: BRAF; colon; immunohistochemistry; morphology; serrated polyp Colorectal cancer is one of the leading causes of cancer death worldwide. Although increased use of screening and surveillance, as well as detection and the removal of conventional adenomas, has led to a reduction in the incidence and mortality of this disease, this effect is mainly limited to distal colorectal cancer. 1-5 However, difficulties remain in the prevention of proximal colorectal cancer.A recent study suggested that colorectal cancers of the proximal colon develop in a significantly shorter period of time than those in the distal colon, after a patient has had a negative colonoscopy. 2,3 Thus, there is a need for improved and targeted identification of neoplastic precursor lesions in the proximal colon.Colorectal cancer arises from several different types of precursor lesions. In the conventional pathway, carcinomas develop from adenomas via biallelic APC (adenomatous polyposis coli) mutations 6 and are reinforced by KRAS mutatio...

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“…Very specifi c to serrated polyps is a BRAF and KRAS genes mutation. It was noted that frequently BRAF mutated in serrated aberrant crypt foci (62 %) [47], microvesicular HP (70-76 %) [46], borderline SSA (80 %) [48], SSA (61-100 %) [49] and SSA with cytological dysplasia or invasive cancer (64-100 %) [50]. The BRAF mutations is not typical goblet cells, but it was noted that KRAS mutated in 50 % of cases of hyperplastic polyps [46].…”

Section: Molecular Features Of the Serrated Pathwaymentioning

confidence: 99%

Serrated polyps as precursor lesions of colorectal cancer: current status and future directions. Mini-review.

Kuzo

2016

Patologìâ

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Early diagnosis of colorectal cancer (CRC) is a very urgent problem, since this disease has second place among women and the third one among men in the structure of cancer pathology. According to recent data, CRC should be considered as a heterogeneous multifactorial family of diseases with different variants.Serrated polyps of the colon are obligate precancerous condition, which can transform into cancer due to genetic aberrations. Serrated polyps are a heterogeneous group of formations with different ways of appearance and potential malignancy. They are divided into major subtypes: hyperplastic polyps, sessile serrated adenoma/polyp and traditional serrated adenoma.The purpose of the study was the analysis of current data about mechanisms of formation and malignization of serrated colonic polyps.The relationship between the localization of serrated polyps and their morphology was identifi ed. Polyps located in the proximal colon are characterized by a more expressed degree of serration in the basal segment of crypts compared with polyps located in the distal part of the colon. The difference between the proximal and distal localization was confi rmed by molecular genetic testing: the majority of proximal serrated polyps develops after BRAF mutations, and the majority of polyps with distal localization develops after a KRAS mutation.It is known that a key role in the excessive proliferation and inhibition of apoptosis in the process of malignant transformation of serrated polyps is provided by the combination of different types of genome damage, both genetic and epigenetic. Molecular changes are already present in the early stages of cell dysplasia in serrated colon polyps, and their nature determines the malignant potential.Conclusions. A thorough study of the molecular mechanisms of progression along the serrated pathway and transformation of serrated polyps in the CRC opens up prospects for the development of guidelines for patient management in order to prevent the development of serrated pathway cancers. Зубчасті поліпи як прекурсор розвитку раку товстої кишки: сучасний погляд і перспективи. Міні-огляд І. О. КузьоСвоєчасна діагностика раннього раку товстої кишки є вкрай актуальним питанням сучасності, оскільки це захворювання посідає друге місце серед жінок і третє серед чоловіків у структурі онкологічної патології. Згідно з результатами останніх досліджень, рак товстої кишки слід розглядати як гетерогенну, мультифактор-зумовлену групу захворювань із різними варіан-тами перебігу.Зубчасті поліпи товстої кишки є облігатним передраковим станом. У зв'язку з цим у світі активно вивчаються молекуляр-но-генетичні та імуноморфологічні аспекти їхнього злоякісного потенціалу. Сьогодні дослідники визнають: зубчасті поліпи товстої кишки можуть малігнізуватися шляхом послідовної трансформації, що зумовлена генетичними абераціями.Мета роботи -аналіз сучасних даних щодо механізмів формування та малігнізації зубчастих поліпів товстої кишки. Зубчасті поліпи є гетерогенною групою утворень, що мають різні шляхи розвитку та з...

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Qualities of sessile serrated adenoma/polyp/lesion and its borderline variant in the context of synchronous colorectal carcinoma

Abstract: BSSA/P/L was like SSA/P/L in most respects. The lower SCRC prevalence of BSSA/P/L could fit the idea of BSSA/P/L as a precursor to SSA/P/L, a notion that deserves attention when formulating guidelines for CRC screening.

Cited by 22 publications

References 46 publications

The stem cell marker CD133 is highly expressed in sessile serrated adenoma and its borderline variant compared with hyperplastic polyp

The stem cell marker CD133 is highly expressed in sessile serrated adenoma and its borderline variant compared with hyperplastic polyp

Improved molecular classification of serrated lesions of the colon by immunohistochemical detection of BRAF V600E

Serrated polyps as precursor lesions of colorectal cancer: current status and future directions. Mini-review.

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