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Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis.

Published on Mar 7, 2014in Modern Pathology6.365
· DOI :10.1038/MODPATHOL.2014.35
Jia-Huei Tsai13
Estimated H-index: 13
(NTU: National Taiwan University),
Jau-Yu Liau17
Estimated H-index: 17
(NTU: National Taiwan University)
+ 4 AuthorsYung-Ming Jeng55
Estimated H-index: 55
(NTU: National Taiwan University)
Abstract
Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis
  • References (35)
  • Citations (44)
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References35
Newest
#1Mark Bettington (UQ: University of Queensland)H-Index: 15
#2Neal I. Walker (UQ: University of Queensland)H-Index: 35
Last. Vicki L. J. Whitehall (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 31
view all 6 authors...
Approximately 30% of colorectal carcinomas develop via a serrated neoplasia pathway, named for the pattern of crypts in the precursor polyps. Molecular abnormalities consistently involve methylation of CpG islands [CpG island methylator phenotype (CIMP)] of low degree (CIMP-L) or high degree (CIMP-H), and activating mutations of the mitogen-activated protein kinase pathway components BRAF or KRAS. Microsatellite instability (MSI) of a high level (MSI-H) is often present, allowing for a molecular...
247 CitationsSource
#1Christophe Rosty (UQ: University of Queensland)H-Index: 46
#2Joanne P. Young (UQ: University of Queensland)H-Index: 60
Last. Daniel D. Buchanan (QIMR: QIMR Berghofer Medical Research Institute)H-Index: 50
view all 19 authors...
Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features
93 CitationsSource
Molecular characterization has been extensively studied in serrated polyps but very little is known in serrated adenocarcinomas (SACs). We analyzed the incidence of KRAS, BRAF and PIK3CA mutations, microsatellite instability (MSI) status and loss of the DNA repair proteins MLH1, MSH2, MSH6 and MGMT in a series of 89 SAC, 81 matched conventional carcinomas (CC) and 13 sporadic colorectal cancer showing histological and molecular features of high-level MSI (sMSI-H). Our results demonstrate that KR...
35 CitationsSource
#1Douglas K. Rex (IU: Indiana University)H-Index: 91
#2Dennis J. Ahnen (University of Colorado Denver)H-Index: 60
Last. James M. Church (Cleveland Clinic)H-Index: 77
view all 19 authors...
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was he...
649 CitationsSource
#1Baojin Fu (Johns Hopkins University)H-Index: 11
#2Shinichi Yachida (Johns Hopkins University)H-Index: 31
Last. Christine A. Iacobuzio-Donahue (Johns Hopkins University)H-Index: 78
view all 6 authors...
Traditional serrated adenomas (TSAs) are a type of colorectal polyp with neoplastic potential. Immunohistochemical analysis and sequencing were performed on 24 TSAs from 23 patients to characterize the molecular genetics of TSAs. Abnormal Ki-67 and p53 labeling were observed in 7 (29%) of 24 and 6 (25%) of 24 TSAs, respectively; both types were significantly associated with the presence of conventional epithelial dysplasia (P = .0005 and P = .0001, respectively). Activating KRAS mutation was ide...
55 CitationsSource
Abstract Context.—In addition to chromosomal instability and microsatellite instability (MSI), a third pathway, epigenetic instability, has been implicated in progression to colorectal carcinogenes...
61 CitationsSource
Adenocarcinoma of the large intestine can no longer be considered one disease but rather a family of diseases with different precursor lesions, different molecular pathways, and different end-stage carcinomas with varying prognoses. Approximately 60% of colorectal carcinomas arise from conventional adenomas via the suppressor pathway leading to microsatellite stable carcinomas. These carcinomas represent the pathway that has been the target of screening and prevention programs to date. However, ...
421 CitationsSource
#1Daniela Aust (TUD: Dresden University of Technology)H-Index: 33
#2Gustavo B. Baretton (TUD: Dresden University of Technology)H-Index: 28
Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas—because of their cytological atypia—were recognized as the precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression mainly because hyperplastic polyps are missing cytological atypia. Meanwhile, it is recognized that the lesions, formerly classified as hyperplastic, repre...
84 CitationsSource
#1Barbara A. Leggett (Royal Brisbane and Women's Hospital)H-Index: 69
#1Barbara Leggette (Royal Brisbane and Women's Hospital)
Last. Vicki L. J. Whitehall (Queensland Health)H-Index: 31
view all 2 authors...
The "serrated neoplastic pathway" describes the progression of serrated polyps, including sessile serrated adenomas and traditional serrated adenomas, to colorectal cancer. The recognition of this pathway during the last 15 years has led to a paradigm shift in our understanding of the molecular basis of colorectal cancer and significant changes in clinical practice. These findings are particularly relevant to prevention of interval cancers through colonoscopy surveillance programs—an important i...
566 CitationsSource
#1Kyoung-Mee Kim (SMC: Samsung Medical Center)H-Index: 45
#1Yang Soo KimH-Index: 32
Last. Robert D. OdzeH-Index: 71
view all 5 authors...
The pathogenesis and risk of malignancy of traditional serrated adenomas (TSAs) are unclear. In North America, TSAs are relatively uncommon, occur mainly in the left colon, and in some studies, have not been shown to have a strong association with hyperplastic polyp (HPP) or sessile polyp adenoma (SSA) precursor lesions. In the Far East, and particularly in Korea, TSAs are more common and occur both in the left and right colon. However, the pathogenesis of TSAs in Korean patients, and the simila...
77 CitationsSource
Cited By44
Newest
#1Hongxing Gui (HUP: Hospital of the University of Pennsylvania)H-Index: 1
#2Michael A. Husson (HUP: Hospital of the University of Pennsylvania)H-Index: 1
Last. Rifat Mannan (HUP: Hospital of the University of Pennsylvania)H-Index: 1
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Traditional serrated adenoma was first reported by Longacre and Fenoglio-Presier in 1990. Their initial study described main features of this lesion, but the consensus diagnostic criteria were not widely adopted until recently. Traditional serrated adenoma presents with grossly protuberant configuration and pinecone-like appearance upon endoscopy. Histologically, it is characterized by ectopic crypt formation, slit-like serration, eosinophilic cytoplasm and pencillate nuclei. Although much is no...
1 CitationsSource
#1Won-Tak Choi (UCSF: University of California, San Francisco)H-Index: 12
#2Masato Yozu (Middlemore Hospital)H-Index: 5
Last. Gregory Y. LauwersH-Index: 80
view all 8 authors...
Several types of nonconventional dysplasia have been recently described in inflammatory bowel disease (IBD). However, strict morphologic criteria are lacking, and their clinicopathologic features (including potential association with conventional dysplasia and/or colorectal cancer [CRC]) are poorly understood. A total of 106 dysplastic or serrated lesions in 58 IBD patients with CRC were retrospectively identified from five institutions. Thirty-six cases of nonconventional dysplasia were identif...
1 CitationsSource
#1Pierre SohierH-Index: 2
#2Romain Sanson (Paris V: Paris Descartes University)H-Index: 1
Last. Benoit TerrisH-Index: 57
view all 13 authors...
Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label-free quantification (LF...
Source
#1Gregory Miller (UQ: University of Queensland)H-Index: 9
#2Cheng Liu (UQ: University of Queensland)H-Index: 8
Last. Christophe Rosty (UQ: University of Queensland)H-Index: 46
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Summary Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma (CRC). The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens. The 27 colectomy lesions presented predominantly as ill-defined areas with granular appearance, with a median size of 15 mm, located through...
Source
#1Hiroyoshi Nakanishi (Kanazawa University)H-Index: 7
#2Takeshi SawadaH-Index: 5
Last. Naoki TakahashiH-Index: 40
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Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and micr...
Source
#1Shigeki SekineH-Index: 30
#2Satoshi Yamashita (Epigenomics AG)H-Index: 22
Last. Yutaka SaitoH-Index: 58
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Background Traditional serrated adenoma (TSA) is the least common type of colorectal serrated polyp, which exhibits considerable morphological and molecular diversity.
2 CitationsSource
#1Akiko ChinoH-Index: 7
#1Akiko ChinoH-Index: 13
Last. Satoshi NagayamaH-Index: 37
view all 9 authors...
OBJECTIVES: Serrated lesions of the colorectum often have complex histological morphology, and some groups include subtypes with different molecular biology. This study aimed to characterize serrated lesions with heterogeneous histology that was dominated by a traditional serrated adenoma (TSA) component. METHODS: Representative lesions were selected based on both endoscopic and histological features. If a lesion had more than one component, each of the different structural parts was considered ...
2 CitationsSource
#1Fatima Domenica Elisa De Palma (University of Naples Federico II)H-Index: 3
#2Valeria D’Argenio (University of Naples Federico II)H-Index: 15
Last. F. Salvatore (University of Naples Federico II)H-Index: 89
view all 6 authors...
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 morphol...
10 CitationsSource
#1Aoife J McCarthy (UHN: University Health Network)H-Index: 3
#2Stefano Serra (UHN: University Health Network)H-Index: 34
Last. Runjan Chetty (UHN: University Health Network)H-Index: 2
view all 3 authors...
Objective To provide an overview of the pathology and molecular pathogenesis of traditional serrated adenomas (TSA). Design Describe the morphology and molecules that play a role in their pathogenesis. Results These exuberant polypoid lesions are typified by tall cells with deeply eosinophilic cytoplasm, elongated nuclei bearing delicate chromatin, ectopic crypt foci, deep clefting of the lining mucosa and an overall resemblance to small bowel mucosa. Broadly, TSAs arise via three mechanisms. Th...
4 CitationsSource
#1Runjan Chetty (UHN: University Health Network)H-Index: 2
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