Prognostic Impact of Src, CDKN1B, and JAK2 Expression in Metastatic Breast Cancer Patients Treated with Trastuzumab.

Journal

Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619

Informations de publication

Date de publication:
May 2019
Historique:
received: 11 12 2018
accepted: 21 02 2019
pubmed: 17 3 2019
medline: 17 3 2019
entrez: 17 3 2019
Statut: ppublish

Résumé

Src, CDKN1B, and JAK2 play a crucial role in the coordination of cell signaling pathways. In the present study, we aim to investigate the prognostic significance of these biomarkers in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab (T). Formalin-fixed paraffin-embedded tumor tissue samples from 197 patients with HER2-positive MBC treated with T were retrospectively collected. All tissue samples were centrally assessed for ER, PgR, Ki67, HER2, and PTEN protein expression; EGFR gene amplification; PI3KCA mutational status; and tumor-infiltrating lympocytes density. Src, CDKN1B, and JAK2 mRNA expression was evaluated using quantitative reverse transcription-polymerase chain reaction. Only 133 of the 197 patients (67.5%) were found to be HER2-positive by central assessment. CDKN1B mRNA expression was strongly correlated with Src (rho = 0.71) and JAK2 (rho = 0.54). In HER2-positive patients, low CDKN1B conferred higher risk for progression [hazard ratio (HR) = 1.58, 95% confidence interval (CI) 1.08-2.32, P = .018]. In HER2-negative patients, low Src was associated with longer survival (HR = 0.56, 95% CI 0.32-0.99, P = .045). Upon multivariate analyses, only low CDKN1B and JAK2 mRNA expression remained unfavorable factors for PFS in de novo and relapsed (R)-MBC patients, respectively (HR = 2.36, 95% CI 1.01-5.48, P = .046 and HR = 1.76, 95% CI 1.01-3.06, P = .047, respectively). Low CDKN1B and JAK2 mRNA expressions were unfavorable prognosticators in a cohort of T-treated MBC patients. Our results suggest that CDKN1B and JAK2, if validated, may serve as prognostic factors potentially implicated in T resistance, which seems to be associated with distinct pathways in de novo and R-MBC.

Sections du résumé

BACKGROUND BACKGROUND
Src, CDKN1B, and JAK2 play a crucial role in the coordination of cell signaling pathways. In the present study, we aim to investigate the prognostic significance of these biomarkers in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab (T).
METHODS METHODS
Formalin-fixed paraffin-embedded tumor tissue samples from 197 patients with HER2-positive MBC treated with T were retrospectively collected. All tissue samples were centrally assessed for ER, PgR, Ki67, HER2, and PTEN protein expression; EGFR gene amplification; PI3KCA mutational status; and tumor-infiltrating lympocytes density. Src, CDKN1B, and JAK2 mRNA expression was evaluated using quantitative reverse transcription-polymerase chain reaction.
RESULTS RESULTS
Only 133 of the 197 patients (67.5%) were found to be HER2-positive by central assessment. CDKN1B mRNA expression was strongly correlated with Src (rho = 0.71) and JAK2 (rho = 0.54). In HER2-positive patients, low CDKN1B conferred higher risk for progression [hazard ratio (HR) = 1.58, 95% confidence interval (CI) 1.08-2.32, P = .018]. In HER2-negative patients, low Src was associated with longer survival (HR = 0.56, 95% CI 0.32-0.99, P = .045). Upon multivariate analyses, only low CDKN1B and JAK2 mRNA expression remained unfavorable factors for PFS in de novo and relapsed (R)-MBC patients, respectively (HR = 2.36, 95% CI 1.01-5.48, P = .046 and HR = 1.76, 95% CI 1.01-3.06, P = .047, respectively).
CONCLUSIONS CONCLUSIONS
Low CDKN1B and JAK2 mRNA expressions were unfavorable prognosticators in a cohort of T-treated MBC patients. Our results suggest that CDKN1B and JAK2, if validated, may serve as prognostic factors potentially implicated in T resistance, which seems to be associated with distinct pathways in de novo and R-MBC.

Identifiants

DOI: 10.1016/j.tranon.2019.02.010 PMID: 30877976 PMC: PMC6423363
pubmed: 30877976
pii: S1936-5233(18)30621-1
doi: 10.1016/j.tranon.2019.02.010
pmc: PMC6423363
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

739-748

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Panagiota Economopoulou (P)

Second Department of Internal Medicine, Attikon University Hospital, 1 Rimini St 12462, Haidari, Athens, Greece. Electronic address: panagiota_oiko@hotmail.com.

Vassiliki Kotoula (V)

Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, University Campus, Building 17B, 54006, Thessaloniki, Greece; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, Building 17B, 54006, Thessaloniki, Greece. Electronic address: vkotoula@auth.gr.

Georgia-Angeliki Koliou (GA)

Section of Biostatistics, Hellenic Cooperative Oncology Group, 18 Hatzikonstanti St, 11524, Athens, Greece. Electronic address: g_koliou@hecog.ondsl.gr.

Kyriaki Papadopoulou (K)

Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, Building 17B, 54006, Thessaloniki, Greece. Electronic address: kyriakipapadopoulou@hotmail.com.

Christos Christodoulou (C)

Second Department of Medical Oncology, Metropolitan Hospital, 9 Ethnarchou Makariou St, 185 47, Piraeus, Greece. Electronic address: c_christodoulou@yahoo.gr.

George Pentheroudakis (G)

Department of Medical Oncology, Ioannina University Hospital, Leof. Stavrou Niarchou, 45500, Ioannina, Greece. Electronic address: gpenther@cc.uoi.gr.

Georgios Lazaridis (G)

Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Ring Road, Nea Efkarpia, 56450, Thessaloniki, Greece.

Petroula Arapantoni-Dadioti (P)

Department of Pathology, Henry Dunant Hospital, 107 Mesogion Av, 11526, Athens, Greece.

Angelos Koutras (A)

Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Panepistimioupoli Patron, 26504, Patras, Greece. Electronic address: angkoutr@otenet.gr.

Dimitris Bafaloukos (D)

First department of Medical Oncology, Metropolitan Hospital, 9 Ethnarchou Makariou St, 185 47, Piraeus, Greece. Electronic address: dimmp@otenet.gr.

Pavlos Papakostas (P)

Oncology Unit, Hippokration Hospital, 114 Vasilissis Sofias Av, 11527, Athens, Greece. Electronic address: p.papakostas@gmail.com.

Helen Patsea (H)

Department of Pathology, IASSO General Hospital, 264 Mesogion Av, 15562, Athens, Greece.

Kitty Pavlakis (K)

Pathology Department, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.

Dimitrios Pectasides (D)

Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, 114 Vasilissis Sofias Av, 11527, Athens, Greece. Electronic address: pectasid@otenet.gr.

Athanasios Kotsakis (A)

Department of Medical Oncology, University General Hospital of Heraklion, Voutes, 71110, Crete, Greece. Electronic address: thankotsakis@hotmail.com.

Evangelia Razis (E)

Third Department of Medical Oncology, Hygeia Hospital, 4 Erithrou Stavrou St, Marousi, 15123, Athens, Greece. Electronic address: e.razis@hygeia.gr.

Gerasimos Aravantinos (G)

Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.

Epaminondas Samantas (E)

Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Timiou Stavrou, 14564, Kifisia, Athens, Greece. Electronic address: epsam@otenet.gr.

Konstantine T Kalogeras (KT)

Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, Building 17B, 54006, Thessaloniki, Greece; Translational Research Section, Hellenic Cooperative Oncology Group, 18 Hatzikonstanti St, 11524, Athens, Greece. Electronic address: k_kalogeras@hecog.ondsl.gr.

Theofanis Economopoulos (T)

Second Department of Internal Medicine, Attikon University Hospital, 1 Rimini St 12462, Haidari, Athens, Greece. Electronic address: economopoulosth@ath.forthnet.gr.

Amanta Psyrri (A)

Second Department of Internal Medicine, Attikon University Hospital, 1 Rimini St 12462, Haidari, Athens, Greece. Electronic address: psyrri237@yahoo.com.

George Fountzilas (G)

Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, University Campus, Building 17B, 54006, Thessaloniki, Greece; Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece. Electronic address: fountzil@auth.gr.

Classifications MeSH