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J Transl Med. 2017 Feb 13;15(1):30. doi: 10.1186/s12967-017-1134-7.

Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.

Author information

1
Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. psyrri237@yahoo.com.
2
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece.
3
Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
4
STRATIFYER Molecular Pathology GmbH, Cologne, Germany.
5
Department of Biostatistics, Health Data Specialists Ltd, Athens, Greece.
6
Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloníki, Greece.
7
Department of Pathology, Ioannina University Hospital, Ioannina, Greece.
8
Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
9
Department of Medical Oncology, Faculty of Medicine, Papageorgiou Hospital, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloníki, Greece.
10
First Department of Medicine, Laiko General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
11
Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece.
12
Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
13
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
14
Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece.
15
First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
16
Department of Pathology, Micromedica Labs, Athens, Greece.
17
Department of Pathology, Alexandra Hospital, Athens, Greece.
18
Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece.
19
Oncology Unit, Hippokration Hospital, Athens, Greece.
20
Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
21
Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece.
22
Aristotle University of Thessaloniki, Thessaloníki, Greece.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Breast cancer; IHC; Osteopontin; Prognostic value; Survival; mRNA; qRT-PCR

PMID:
28193231
PMCID:
PMC5304396
DOI:
10.1186/s12967-017-1134-7
[Indexed for MEDLINE]
Free PMC Article

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