Evidence map›Paper›PMID 27835607›Full record

ArticleOncotarget2016

p16 overexpression and 9p21 deletion are linked to unfavorable tumor phenotype in breast cancer.

Patrick Lebok, Magdalena Roming, Martina Kluth, Christina Koop, Cansu Özden, Berivan Taskin, Khakan Hussein, Annette Lebeau, Isabell Witzel, Linn Wölber and 12 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-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

25 citing papers in PubMed, 44 citations in OpenAlex.

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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

22 authors at 7 institutions in 2 countries.

Patrick LebokInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Magdalena RomingInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Martina KluthInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christina KoopInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cansu ÖzdenInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Berivan TaskinInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Khakan HusseinInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Annette LebeauInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Isabell WitzelDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Linn WölberDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Stefan GeistDepartment of Gynecology, Regio Clinic Pinneberg, Pinneberg, Germany.
Peter PaluchowskiDepartment of Gynecology, Regio Clinic Pinneberg, Pinneberg, Germany.
Christian WilkeDepartment of Gynecology, Regio Clinic Elmshorn, Elmshorn, Germany.
Uwe HeilenkötterDepartment of Gynecology, Clinical Centre Itzehoe, Itzehoe, Germany.
Volkmar MüllerDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Barbara SchmalfeldtDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ronald SimonInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Guido SauterInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Luigi TerraccianoDepartment of Pathology, Basel University Clinics, Basel, Switzerland.
Rainer Horst KrechInstitute of Pathology, Clinical Centre Osnabrück, Osnabrück, Germany.
Albert von der AssenBreast Centre Osnabrück, Osnabrück, Germany.
Eike BurandtInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Universität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DERegio Kliniken · DEHochschule Osnabrück · DEKlinikum Itzehoe · DEOsnabrück University · DEUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Overexpression of the p16 tumor suppressor, but also deletion of its gene locus 9p21, is linked to unfavorable tumor phenotype and poor prognosis in breast cancer. To better understand these contradictory observations, and to clarify the prognostic impact of p16 expression and 9p21 deletion, a tissue microarray (TMA) with 2,197 breast cancers was analyzed by fluorescence in-situ hybridization and immunohistochemistry (FISH) for 9p21 deletion and p16 expression. p16 immunostaining was weak in 25.6%, moderate in 7.1%, and strong in 12.7% of 1,684 evaluable cancers. Strong p16 staining was linked to advanced tumor stage (p = 0.0003), high-grade (p < 0.0001), high tumor cell proliferation (p < 0.0001), negative hormone receptor (ER/PR) status (p < 0.0001 each), and shorter overall survival (p = 0.0038). 9p21 deletion was found in 15.3% of 1,089 analyzable breast cancers, including 1.7% homozygous and 13.6% heterozygous deletions. 9p21 deletion was linked to adverse tumor features, including high-grade (p < 0.0001) and nodal positive cancers (p = 0.0063), high cell proliferation (p < 0.0001), negative hormone receptor (ER/PR) status (p ≤ 0.0006), and HER2 amplification (p = 0.0078). Patient outcome was worse in 9p21 deleted than in undeleted cancers (p = 0.0720). p16 expression was absent in cancers harboring homozygous 9p21 deletions, but no difference in p16 expression was found between cancers with (59.2% p16 positive) and without heterozygous 9p21 deletion (51.3% p16 positive, p = 0.0256). In summary, p16 expression is unrelated to partial 9p21 deletion, but both alterations are linked to aggressive breast cancer phenotype. High-level p16 expression is a strong predictor of unfavorable disease course in breast cancer.

Indexed as

Biomarkers, TumorChromosomes, Human, Pair 9Gene DeletionBreast NeoplasmsCell ProliferationChromosome DisordersCyclin-Dependent Kinase Inhibitor p16FemaleGenetic Predisposition to DiseaseHeterozygoteHomozygoteHumansImmunohistochemistryIn Situ Hybridization, FluorescenceKaplan-Meier EstimateLymphatic MetastasisBiomarkers, TumorCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p169p21 deletionbreast cancerCDKN2Ap16 expressionTMA

Identifiers

PMID27835607
PMCPMC5348395
OpenAlexW2551420967

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Registered trials

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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.