Evidence map›Paper›PMID 25216220›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2015

A clinicopathological and molecular analysis of 200 traditional serrated adenomas.

Mark L Bettington, Neal I Walker, Christophe Rosty, Ian S Brown, Andrew D Clouston, Diane M McKeone, Sally-Ann Pearson, Kerenaftali Klein, Barbara A Leggett, Vicki L J Whitehall

Abstract read
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Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed.

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  17. Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling.Pathobiology : journal of immunopathology, molecular and cellular biology · 2024
    Article
  18. Review
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Mark L Bettington1] The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia [2] The School of Medicine, The University of Queensland, Brisbane, QLD, Australia [3] Envoi Specialist Pathologists, Brisbane, QLD, Australia.
Neal I Walker1] The School of Medicine, The University of Queensland, Brisbane, QLD, Australia [2] Envoi Specialist Pathologists, Brisbane, QLD, Australia.
Christophe Rosty1] The School of Medicine, The University of Queensland, Brisbane, QLD, Australia [2] Envoi Specialist Pathologists, Brisbane, QLD, Australia [3] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Carlton, VIC, Australia.
Ian S Brown1] Envoi Specialist Pathologists, Brisbane, QLD, Australia [2] Department of Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
Andrew D Clouston1] The School of Medicine, The University of Queensland, Brisbane, QLD, Australia [2] Envoi Specialist Pathologists, Brisbane, QLD, Australia [3] Department of Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
Diane M McKeoneThe Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Sally-Ann PearsonThe Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Kerenaftali KleinStatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Barbara A Leggett1] The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia [2] The School of Medicine, The University of Queensland, Brisbane, QLD, Australia [3] The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Vicki L J Whitehall1] The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia [2] The School of Medicine, The University of Queensland, Brisbane, QLD, Australia [3] Department of Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The traditional serrated adenoma is the least common colorectal serrated polyp. The clinicopathological features and molecular drivers of these polyps require further investigation. We have prospectively collected a cohort of 200 ordinary and advanced traditional serrated adenomas and performed BRAF and KRAS mutational profiling, CpG island methylator phenotype analysis, and immunohistochemistry for a panel of 7 antibodies (MLH1, β-catenin, p53, p16, Ki67, CK7, and CK20) on all cases. The mean age of the patients was 64 years and 50% were female. Of the polyps, 71% were distal. Advanced histology (overt dysplasia or carcinoma) was present in 19% of cases. BRAF mutation was present in 67% and KRAS mutation in 22%. BRAF mutant traditional serrated adenomas were more frequently proximal (39% versus 2%; P≤0.0001), were exclusively associated with a precursor polyp (57% versus 0%; P≤0.0001), and were more frequently CpG island methylator phenotype high (60% versus 16%; P≤0.0001) than KRAS mutant traditional serrated adenomas. Advanced traditional serrated adenomas retained MLH1 expression in 97%, showed strong p53 staining in 55%, and nuclear β-catenin staining in 40%. P16 staining was lost in the advanced areas of 55% of BRAF mutant traditional serrated adenomas compared with 10% of the advanced areas of KRAS mutant or BRAF/KRAS wild-type traditional serrated adenomas. BRAF and KRAS mutant traditional serrated adenomas are morphologically related but biologically disparate polyps with distinctive clinicopathological and molecular features. The overwhelming majority of traditional serrated adenomas retain mismatch repair enzyme function indicating a microsatellite-stable phenotype. Malignant progression occurs via TP53 mutation and Wnt pathway activation regardless of mutation status. However, CDKN2A (encoding the p16 protein) is silenced nearly exclusively in the advanced areas of the BRAF mutant traditional serrated adenomas. Thus, the BRAF mutant traditional serrated adenoma represents an important precursor of the aggressive BRAF mutant, microsatellite-stable subtype of colorectal carcinoma.

Indexed as

AdenomaAgedBiomarkers, TumorColonic PolypsColorectal NeoplasmsDNA MethylationDNA Mutational AnalysisFemaleHumansImmunohistochemistryMaleMiddle AgedProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras ProteinsBiomarkers, TumorBRAF protein, humanKRAS protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID25216220

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.