title: Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.
abstract: The shift towards an earlier diagnosis of breast cancer (BC) highlights the need for biomarkers that would identify patients at risk for relapse and metastatic spread and indicate the potential value of additional treatment strategies. Osteopontin (OPN) is a matricellular protein that has been suggested to be a potential biomarker in BC. In the present study, we used archived BC patient samples to assess the clinical utility of OPN.
  
  
  
  Formalin-fixed paraffin-embedded tumor tissue samples from 975 patients were collected from two large phase III randomized adjuvant chemotherapy trials (HE10/97 and HE10/00) that included patients with high risk BC. All tissue samples were assessed for ER, PgR, Ki67 and HER2 protein expression. OPN protein and mRNA expression was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, respectively.
  
  
  
  OPN mRNA expression data were available for 814 patients, whereas OPN protein expression data were available for 546 patients. The majority of patients were ER/PgR-positive (78.3%), HER2-negative (76.5%) and Ki67-positive (55.2%) and had received adjuvant radiation therapy (76.8%) and hormonal therapy (81.1%). OPN mRNA expression was significantly associated with age (60.9% in high OPN tumors vs. 54.1% in low OPN tumors, p = 0.047), ER/PgR-negative status (25.7 vs. 17.2%, p = 0.004) and BC subtypes (p = 0.021). In addition, high OPN mRNA expression was significantly associated with reduced DFS (HR 1.26, 95% CI 1.00-1.59, Wald's p = 0.050) and OS (HR 1.37, 95% CI 1.05-1.78, p = 0.019), while it retained its prognostic significance for both DFS (HR 1.39, 95% CI 1.10-1.77, p = 0.007) and OS (HR 1.54, 95% CI 1.61-2.05, p = 0.003) in the multivariate analysis.
  
  
  
  We showed that high OPN mRNA expression is associated with decreased DFS and OS in a large cohort of BC patients treated with adjuvant chemotherapy in a clinical trial setting. Our results suggest that OPN may serve as a prognostic factor and a potential target for therapy. Trial registration Australian New Zealand Clinical Trials Registry; HE10/97 ACTRN12611000506998; HE10/00 ACTRN12609001036202.
authors.affiliation: Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. psyrri237@yahoo.com.
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece.|Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
authors.forename: Konstantine T
authors.initials: KT
authors.lastname: Kalogeras
authors.affiliation: STRATIFYER Molecular Pathology GmbH, Cologne, Germany.
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Wirtz
authors.affiliation: Department of Biostatistics, Health Data Specialists Ltd, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kouvatseas
authors.affiliation: Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloníki, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Karayannopoulou
authors.affiliation: Department of Pathology, Ioannina University Hospital, Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Goussia
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Flora
authors.initials: F
authors.lastname: Zagouri
authors.affiliation: STRATIFYER Molecular Pathology GmbH, Cologne, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Veltrup
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Papageorgiou Hospital, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloníki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Timotheadou
authors.affiliation: First Department of Medicine, Laiko General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.affiliation: Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece.
authors.forename: Angelos
authors.initials: A
authors.lastname: Koutras
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Papageorgiou Hospital, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloníki, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Lazaridis
authors.affiliation: Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Christodoulou
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.affiliation: Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Economopoulou
authors.affiliation: First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Laskarakis
authors.affiliation: Department of Pathology, Micromedica Labs, Athens, Greece.
authors.forename: Petroula
authors.initials: P
authors.lastname: Arapantoni-Dadioti
authors.affiliation: Department of Pathology, Ioannina University Hospital, Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Batistatou
authors.affiliation: Department of Pathology, Alexandra Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sotiropoulou
authors.affiliation: Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.affiliation: Oncology Unit, Hippokration Hospital, Athens, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.affiliation: Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
authors.forename: Paris
authors.initials: P
authors.lastname: Kosmidis
authors.affiliation: Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece.|Aristotle University of Thessaloniki, Thessaloníki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D053495:Osteopontin
keywords: Breast cancer; IHC; Osteopontin; Prognostic value; Survival; mRNA; qRT-PCR