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Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer
Department of Urology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.ORCID-id: 0000-0001-5163-5821
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.ORCID-id: 0000-0002-7061-7255
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2023 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 6212, s. 1698-1706Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers.

Material and methods: Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio.

Results: The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel.

Conclusion: PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2023. Vol. 6212, s. 1698-1706
Nyckelord [en]
androgen deprivation therapy, biomarker, docetaxel, Metastatic prostate cancer, prostate specific antigen
Nationell ämneskategori
Urologi och njurmedicin Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:umu:diva-214585DOI: 10.1080/0284186X.2023.2254480ISI: 001068664400001PubMedID: 37713321Scopus ID: 2-s2.0-85171153075OAI: oai:DiVA.org:umu-214585DiVA, id: diva2:1800896
Forskningsfinansiär
Vetenskapsrådet, 2022-00946Cancerfonden, 19-0054Cancerfonden, 19-0053Cancerfonden, 20-1055Cancerfonden, 21-1856Knut och Alice Wallenbergs Stiftelse, 2020.0235ProstatacancerförbundetTillgänglig från: 2023-09-28 Skapad: 2023-09-28 Senast uppdaterad: 2024-02-01Bibliografiskt granskad

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Bergh, AndersThellenberg-Karlsson, CamillaWikström, PernillaJosefsson, Andreas

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PatologiOnkologiWallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)Urologi och andrologi
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