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ErbB2 Receptor Immunoreactivity in Prostate Cancer: Relationship to the Androgen Receptor, Disease Severity at Diagnosis and Disease Outcome
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, e105063- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: ErbB2 is a member of the epidermal growth factor family of tyrosine kinases that is centrally involved in the pathogenesis of prostate cancer and several studies have reported that a high expression of this protein has prognostic value. In the present study, we have investigated whether tumour ErbB2 immunoreactivity (ErbB2-IR) has clinically useful prognostic value, i.e. that it provides additional prognostic information to that provided by routine clinical tests (Gleason score, tumour stage).

METHODOLOGY/PRINCIPAL FINDINGS: ErbB2-IR was measured in a well-characterised tissue microarray of tumour and non-malignant samples obtained at diagnosis. Additionally, mRNA levels of ErbB2-IR in the prostate were determined in the rat following manipulation of circulating androgen levels. Tumour ErbB2-IR was significantly associated with the downstream signalling molecule phosphorylated-Akt and with the cell proliferation marker Ki-67. The significant association of tumour ErbB2-IR with the Gleason score at diagnosis was lost when controlled for the association of both parameters with Ki-67. In the rat prostate, mRNA for ErbB2 was inversely associated with circulating androgen levels. There was no association between ErbB2-IR and the androgen receptor (AR)-IR in the tumours, but an interaction between the two parameters was seen with respect to their association with the tumour stage. Tumour ErbB2-IR was confirmed to be a prognostic marker for disease-specific survival, but it did not provide significant additive information to the Gleason score or to Ki-67.

CONCLUSIONS/SIGNIFICANCE: It is concluded that tumour ErbB2-IR is of limited clinical value as a prognostic marker to aid treatment decisions, but could be of pathophysiological importance in prostate cancer.

Place, publisher, year, edition, pages
PLOS , 2014. Vol. 9, no 9, e105063- p.
National Category
Immunology in the medical area Other Basic Medicine
Identifiers
URN: urn:nbn:se:umu:diva-93295DOI: 10.1371/journal.pone.0105063PubMedID: 25215939OAI: oai:DiVA.org:umu-93295DiVA: diva2:747179
Available from: 2014-09-16 Created: 2014-09-16 Last updated: 2017-12-05Bibliographically approved

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Hammarsten, PeterWinther, JohannaRudolfsson, Stina HHäggström, JennyKaralija, AmarFowler, Christopher

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