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Epithelial and stromal characteristics of primary tumors predict the bone metastatic subtype of prostate cancer and patient survival after androgen-deprivation therapy
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-6347-1999
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.ORCID iD: 0000-0002-2013-0887
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0001-5394-7239
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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 21, article id 5195Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 14, no 21, article id 5195
Keywords [en]
androgen receptor, bone metastases, ERG, Ki67, metastatic subtypes, PDGFRB, prostate cancer, PSA, SDF1, smooth muscle actin
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-201227DOI: 10.3390/cancers14215195ISI: 000880962300001PubMedID: 36358614Scopus ID: 2-s2.0-85141664487OAI: oai:DiVA.org:umu-201227DiVA, id: diva2:1716306
Funder
Swedish Foundation for Strategic Research, RB13-0119Swedish Cancer Society, 19 0053Swedish Cancer Society, 19 0054Swedish Cancer Society, 21 1856Knut and Alice Wallenberg Foundation, KAW 2015.0114Swedish Research Council, 2018-02594Cancerforskningsfonden i Norrland, 22-2302Cancerforskningsfonden i Norrland, 21-2258Available from: 2022-12-05 Created: 2022-12-05 Last updated: 2022-12-05Bibliographically approved

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Wikström, PernillaHalin Bergström, SofiaJosefsson, AndreasSemenas, JuliusNordstrand, AnnikaThysell, ElinCrnalic, SeadWidmark, AndersThellenberg Karlsson, CamillaBergh, Anders

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Wikström, PernillaHalin Bergström, SofiaJosefsson, AndreasSemenas, JuliusNordstrand, AnnikaThysell, ElinCrnalic, SeadWidmark, AndersThellenberg Karlsson, CamillaBergh, Anders
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Cancers
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