Evidence map›Paper›PMID 26021752›Full record

ArticleJournal of translational medicine2015

Evaluation of the prognostic significance of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) validation study.

Angelos Koutras, Konstantine T Kalogeras, Ralph M Wirtz, Zoi Alexopoulou, Mattheos Bobos, Flora Zagouri, Elke Veltrup, Eleni Timotheadou, Helen Gogas, George Pentheroudakis and 9 more

Open access · goldAbstract readValidation Study
In one paragraph

Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

10 citing papers in PubMed, 17 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

19 authors at 11 institutions in 1 country.

Angelos KoutrasDivision of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, 26504, Rio, Greece. angkoutr@otenet.gr.
Konstantine T KalogerasLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, University Campus, Bldg. 17B, 54 006, Thessaloniki, Greece. k_kalogeras@hecog.ondsl.gr.
Ralph M WirtzSTRATIFYER Molecular Pathology GmbH, Werthmannstr. 1c, 50935, Cologne, Germany. ralph.wirtz@stratifyer.de.
Zoi AlexopoulouHealth Data Specialists Ltd, 22 Katehaki Str., 115 25, Athens, Greece. zoi.alexopoulou@heads.gr.
Mattheos BobosLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, University Campus, Bldg. 17B, 54 006, Thessaloniki, Greece. mbobos@auth.gr.
Flora ZagouriDepartment of Clinical Therapeutics, "Alexandra" Hospital, University of Athens School of Medicine, 80 Vasilissis Sofias Av. and Lourou Str., 115 28, Athens, Greece. florazagouri@yahoo.co.uk.
Elke VeltrupSTRATIFYER Molecular Pathology GmbH, Werthmannstr. 1c, 50935, Cologne, Germany. elke.veltrup@stratifyer.de.
Eleni TimotheadouDepartment of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Ring Road, Nea Efkarpia, 56 429, Thessaloniki, Greece. nellitim@doctors.org.uk.
Helen GogasFirst Department of Medicine, "Laiko" General Hospital, University of Athens School of Medicine, 17 Ag. Thoma Str., 115 27, Athens, Greece. hgogas@hol.gr.
George PentheroudakisDepartment of Medical Oncology, Ioannina University Hospital, Niarchou Av., 45 500, Ioannina, Greece. gpenther@otenet.gr.
Nikolaos PisanidisDepartment of Medical Oncology, IKA Hospital, 40 Mavromichali Str., 54248, Thessaloniki, Greece. n.pisanidis@gmail.com.
Christina MagkouPathology Department, "Evangelismos" Hospital, 45 Ipsilantou Str., 106 76, Athens, Greece. cmagkou@yahoo.com.
Christos ChristodoulouSecond Department of Medical Oncology, "Metropolitan" Hospital, 9 Ethnarchou Makariou Str. and El. Venizelou Str., 185 47, Piraeus, Greece. c_christodoulou@yahoo.gr.
Dimitrios BafaloukosFirst Department of Medical Oncology, "Metropolitan" Hospital, 9 Ethnarchou Makariou Str. and El. Venizelou Str., 185 47, Piraeus, Greece. dimmp@otenet.gr.
Pavlos PapakostasOncology Unit, "Hippokration" Hospital, 108 Vas. Sofias Av., 115 27, Athens, Greece. p.papakostas@gmail.com.
Gerasimos AravantinosSecond Department of Medical Oncology, "Agii Anargiri" Cancer Hospital, Noufaron Str. and Timiou Stavrou Str., 145 64, Athens, Greece. garavantinos@yahoo.gr.
Dimitrios PectasidesOncology Section, Second Department of Internal Medicine, "Hippokration" Hospital, 114 Vas. Sofias Av., 115 27, Athens, Greece. pectasid@otenet.gr.
Haralambos P KalofonosDivision of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, 26504, Rio, Greece. kalofonos@upatras.gr.
George FountzilasLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, University Campus, Bldg. 17B, 54 006, Thessaloniki, Greece. fountzil@auth.gr.
Aristotle University of Thessaloniki · GRHippocration General Hospital · GRMetropolitan Hospital · GRUniversity of Patras · GRAlexandra Hospital · GREvangelismos Hospital · GRHellenic Cooperative Oncology Group · GRHospital Agioi Anargyroi · GRNational and Kapodistrian University of Athens · GRPapageorgiou General Hospital · GRUniversity Hospital of Ioannina · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as a validation analysis of another previously published HeCOG study.

methodsRNA was extracted from 663 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples of high-risk early breast cancer patients enrolled in the randomized HE10/00 trial. Relative mRNA expression of all four HER family members was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

resultsIn compliance with our previous study, the overall agreement between qRT-PCR and IHC/FISH for HER2 status determination was good (69%). Likewise, the overall concordance between qRT-PCR and IHC for EGFR status was high (81%). In line with our previously reported data, we demonstrated a positive association between HER2 and HER3 mRNA expression. Similarly, mRNA expression of HER3 and HER4 was positively associated with each other and negatively associated with EGFR. Regarding relationships with clinico-pathological parameters, our findings are also in agreement with our previous results. Generally, increased EGFR and HER2 mRNA expression was related to unfavorable, whereas high HER3 and HER4 mRNA expression was associated with favorable clinico-pathological parameters. In univariate analysis, no significant association between EGFR, HER2 and HER3 mRNA expression and overall survival (OS) or disease-free survival (DFS) was demonstrated. However, high EGFR protein expression was associated with significantly shorter OS (log-rank, p = 0.015). In compliance with our previously published data, increased HER4 mRNA expression had a significantly favorable prognostic value in terms of OS (p = 0.044) and DFS (p = 0.047). In multivariate analysis, among all HER receptors, only EGFR protein expression was found to affect OS (Wald's p = 0.028) and DFS (p = 0.015) independently. Concerning the combined expression of all four HER family receptors, the combination of high EGFR, high HER2, low HER3 and low HER4 mRNA expression was associated with a trend for shorter OS (log-rank, p = 0.065) and significantly worse DFS (p = 0.033), compared with all other co-expression profiles.

conclusionsThese data indicate that qRT-PCR may represent a valid alternative method for evaluating the expression of HER family members in FFPE breast carcinoma tissue samples.

trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12609001036202.

Indexed as

Gene Expression Regulation, NeoplasticAdultAgedBreast NeoplasmsDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleGreeceHumansImmunohistochemistryMiddle AgedPrognosisReceptor, ErbB-3Receptor, ErbB-4Reproducibility of ResultsErb-b2 Receptor Tyrosine KinasesErbB ReceptorsReceptor, ErbB-3Receptor, ErbB-4RNA, Messenger

Identifiers

PMID26021752
PMCPMC4448562
OpenAlexW2115901649

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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.