Evidence map›Paper›PMID 25127237›Full record

ArticlePloS one2014

Reporting tumor molecular heterogeneity in histopathological diagnosis.

Andrea Mafficini, Eliana Amato, Matteo Fassan, Michele Simbolo, Davide Antonello, Caterina Vicentini, Maria Scardoni, Samantha Bersani, Marisa Gottardi, Borislav Rusev and 7 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
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

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Trial
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  4. Why Formalin-fixed, Paraffin-embedded Biospecimens Must Be Used in Genomic Medicine: An Evidence-based Review and Conclusion.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020
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  12. Fhit down-regulation is an early event in pancreatic carcinogenesis.Virchows Archiv : an international journal of pathology · 2017
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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

17 authors at 1 institution in 1 country.

Andrea MafficiniApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Eliana AmatoApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Matteo FassanApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Michele SimboloApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Davide AntonelloApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
Caterina VicentiniApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Maria ScardoniApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Samantha BersaniApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Marisa GottardiApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Borislav RusevApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Giorgio MalpeliApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
Vincenzo CorboApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Stefano BarbiApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Katarzyna O SikoraApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Rita T LawlorApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Giampaolo TortoraDepartment of Medicine, Oncology Unit, University and Hospital Trust of Verona, Verona, Italy.
Aldo ScarpaApplied Research on Cancer Network (ARC-NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
University of Verona · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDetection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples.

aimTo evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular heterogeneity.

methods35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing.

resultsTM-NGS yielded overlapping results on matched fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57%) tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis.

conclusionsTM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy.

Indexed as

Base SequenceClass I Phosphatidylinositol 3-KinasesDNA Mutational AnalysisHigh-Throughput Nucleotide SequencingHumansNeoplasmsParaffin EmbeddingPhosphatidylinositol 3-KinasesProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras ProteinsTissue FixationTumor Suppressor Protein p53Class I Phosphatidylinositol 3-KinasesKRAS protein, humanPhosphatidylinositol 3-KinasesPIK3CA protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras ProteinsTumor Suppressor Protein p53

Identifiers

PMID25127237
PMCPMC4134249
OpenAlexW1986654278

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.