umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 21) Show all publications
Josefsson, A., Damber, J.-E. & Welén, K. (2019). AR-V7 expression in circulating tumor cells as a potential prognostic marker in metastatic hormone-sensitive prostate cancer [Letter to the editor]. Acta Oncologica, 58(11), 1660-1664
Open this publication in new window or tab >>AR-V7 expression in circulating tumor cells as a potential prognostic marker in metastatic hormone-sensitive prostate cancer
2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 11, p. 1660-1664Article in journal, Letter (Refereed) Published
Abstract [en]

Treatment of patients with metastatic hormone-sensitive (mHSPC) depends on androgen deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling. Although the majority of patients respond well to ADT, castration-resistant prostate cancer (CRPC) inevitably develops. Addition of docetaxel, abiraterone acetate, or enzalutamide, to ADT significantly increases cancer-specific survival (CSS) [1–3]. The drawback is that not all patients respond to the therapies equally well and biomarkers to enable personalized treatment are urgently needed. Prostate-specific antigen (PSA) is a powerful biomarker for diagnosis of PC, but there are no validated biomarkers to prognosticate prognosis, let alone prediction of therapy response, of metastatic disease prior to ADT. Mechanisms important for resistance to ADT and development of CRPC include increased AR levels, constitutively active AR variants such as AR-V7, and intratumoral steroid production to sustain AR signaling despite castrate levels of steroids [4–7]. Although these changes mainly have been reported in CRPC, inherent expression could indicate predisposition for CRPC and poor response to ADT and other therapies targeting AR signaling.

To identify patients with optimal therapeutic benefit from drugs with conceptually different targets, their metastatic disease needs to be characterized. Given the difficulty to access metastatic tissue for analysis, circulating tumor cells (CTCs) have a potential to provide phenotypic information of the tumor, in addition to the prognostic value associated with their abundance [8]. We have demonstrated that gene expression in circulating tumor cells (CTCs) reflects the phenotype of prostate cancer metastases [9]. It has also been suggested that detection of AR-V7 mRNA and AR-V7 localization to the nucleus in CTCs predict poor response to drugs targeting the androgen signaling axis, such as abiraterone acetate and enzalutamide, in patients with CRPC [10,11]. Although the biomarker potential of CTCs mostly has been evaluated in CRPC [10,12,13], two studies have described the presence of CTCs as a prognostic marker for overall survival, progression-free survival (PFS), and time to CRPC also in mHSPC [14,15]. In addition, we previously showed that detection of EGFR mRNA in CTCs is a negative prognostic biomarker for CSS in mHSPC [16].

The present study investigates expression of genes associated with development of CRPC [17] for their prognostic value in mHSPC response to ADT. We showed that mRNA for the steroidogenic enzymes AKR1C3 and CYP17A1 can be detected in CTCs in high volume mHSPC, and that the detection of mRNA for AR-V7 in CTCs before ADT has prognostic value.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-162333 (URN)10.1080/0284186X.2019.1637540 (DOI)000478178600001 ()31286815 (PubMedID)2-s2.0-85068650201 (Scopus ID)
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2020-01-09Bibliographically approved
Bovinder Ylitalo, E., Thysell, E., Thellenberg-Karlsson, C., Lundholm, M., Widmark, A., Bergh, A., . . . Wikström, P. (2019). Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens. The Prostate
Open this publication in new window or tab >>Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens
Show others...
2019 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Taxane treatment may be a suitable therapeutic option for patients with castration‐resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR‐Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR‐V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored.

Methods: Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm3. Two cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole‐genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis.

Results: Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1‐CabR1 and 22Rv1‐CabR2, both showed upregulation of the ATP‐binding cassette sub‐family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR‐antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1‐CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment.

Conclusions: Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR‐V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti‐androgens.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
ABCB1, androgen receptor, cabazitaxel, cholesterol, prostate cancer, splice variant
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-167098 (URN)10.1002/pros.23935 (DOI)000500369300001 ()31799745 (PubMedID)
Funder
Swedish Cancer Society, CAN 2013/1324Swedish Cancer Society, CAN 2018/863Swedish Research Council, 2018-02594
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-01-09
Kohestani, K., Wallström, J., Dehlfors, N., Sponga, O. M., Månsson, M., Josefsson, A., . . . Hugosson, J. (2019). Performance and inter-observer variability of prostate MRI (PI-RADS version 2) outside high-volume centres. Scandinavian journal of urology
Open this publication in new window or tab >>Performance and inter-observer variability of prostate MRI (PI-RADS version 2) outside high-volume centres
Show others...
2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Article in journal (Refereed) Epub ahead of print
Abstract [en]

Objective: Despite the growing trend to embrace pre-biopsy MRI in the diagnostic pathway for prostate cancer (PC), its performance and inter-observer variability outside high-volume centres remains unknown. This study aims to evaluate sensitivity of and variability between readers of prostate MRI outside specialized units with radical prostatectomy (RP) specimen as the reference standard.

Materials and methods: Retrospective study comprising a consecutive cohort of all 97 men who underwent MRI and subsequent RP between January 2012 and December 2014 at a private hospital in Sweden. Three readers, blinded to clinical data, reviewed all images (including 11 extra prostate MRI to reduce bias). A tumour was considered detected if the overall PI-RADS v2 score was 3-5 and there was an approximate match (same or neighbouring sector) of tumour sector according to a 24 sector system used for both MRI and whole mount sections.

Results: Detection rate for the index tumour ranged from 67 to 76%, if PI-RADS 3-5 lesions were considered positive and 54-66% if only PI-RADS score 4-5 tumours were included. Detection rate for aggressive tumours (GS >= 4 + 3) was higher; 83.1% for PI-RADS 3-5 and 79.2% for PI-RADS 4-5. The agreement between readers showed average values of 0.41 for PI-RADS score 3-5 and 0.51 for PI-RADS score 4-5.

Conclusions: Prostate MRI evidenced a moderate detection rate for clinically significant PC with a rather large variability between readers. Clinics outside specialized units must have knowledge of their performance of prostate MRI before considering omitting biopsies in men with negative MRI.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Prostatic neoplasms, magnetic resonance imaging, radical prostatectomy, interobserver agreement, observer variation
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-165467 (URN)10.1080/21681805.2019.1675757 (DOI)000493146100001 ()31661357 (PubMedID)
Available from: 2019-12-04 Created: 2019-12-04 Last updated: 2019-12-04
Bratt, O., Holmberg, E., Andrén, O., Carlsson, S., Drevin, L., Johansson, E., . . . Robinsson, D. (2019). The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS). European Urology, 76(4), 461-466
Open this publication in new window or tab >>The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)
Show others...
2019 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, no 4, p. 461-466Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown.

OBJECTIVE: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance.

DESIGN, SETTING, AND PARTICIPANTS: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included.

INTERVENTION: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measure: Gleason grade group ≥2 cancer.

SECONDARY OUTCOMES: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied.

RESULTS AND LIMITATIONS: Gleason grade group ≥2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p=0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p=0.004) and for Gleason grade group ≥2 cancer 2.3 (95% CI 1.2-4.4, p=0.015) per 0.1-ng/ml/cm3 increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used.

CONCLUSIONS: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy.

PATIENT SUMMARY: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Active surveillance, Biopsy, Prostate cancer, Randomised clinical trial
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-163538 (URN)10.1016/j.eururo.2019.02.035 (DOI)000487930900025 ()30878303 (PubMedID)2-s2.0-85062811212 (Scopus ID)
Available from: 2019-09-25 Created: 2019-09-25 Last updated: 2019-10-24Bibliographically approved
Josefsson, A., Larsson, K., Månsson, M., Björkman, J., Rohlova, E., Åhs, D., . . . Welén, K. (2018). Circulating tumor cells mirror bone metastatic phenotype in prostate cancer. OncoTarget, 9(50), 29403-29413
Open this publication in new window or tab >>Circulating tumor cells mirror bone metastatic phenotype in prostate cancer
Show others...
2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 50, p. 29403-29413Article in journal (Refereed) Published
Abstract [en]

Circulating tumor cells (CTCs) are promising biomarkers in prostate cancer (PC) because they derive from primary tumor and metastatic tissues. In this study, we used quantitative real-time PCR (qPCR) to compare the expression profiles of 41 PC-related genes between paired CTC and spinal column metastasis samples from 22 PC patients that underwent surgery for spinal cord compression. We observed good concordance between the gene expression profiles in the CTC and metastasis samples in most of the PC patients. Expression of nine genes (AGR2, AKR1C3, AR, CDH1, FOLH1, HER2, KRT19, MDK, and SPINK1) showed a significant correlation between the CTC and metastasis samples. Hierarchical clustering analysis showed a similar grouping of PC patients based on the expression of these nine genes in both CTC and metastasis samples. Our findings demonstrate that CTCs mirror gene expression patterns in tissue metastasis samples from PC patients. Although low detection frequency of certain genes is a limitation in CTCs, our results indicate the potential for CTC phenotyping as a tool to improve individualized therapy in metastatic prostate cancer.

Keywords
circulating tumor cells, liquid biopsies, skeletal metastases of prostate cancer
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-159988 (URN)10.18632/oncotarget.25634 (DOI)30034626 (PubMedID)
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-13Bibliographically approved
Josefsson, A., Linder, A., Flondell Site, D., Canesin, G., Stiehm, A., Anand, A., . . . Welén, K. (2017). Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer. The Prostate, 77(8), 849-858
Open this publication in new window or tab >>Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer
Show others...
2017 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 8, p. 849-858Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC).

METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study. CTCs were analysed for expression of PSA prostate specific membrane antigen (PSMA) and epidermal growth factor receptor (EGFR) before and three months after ADT and related to progression.

RESULTS: At inclusion, 46 out of 53 patients (87%) were CTC-positive with a sensitivity and specificity for distant metastases (M1) of 98% and 75%, respectively. In patients with M1-disease, EGFR-detection in CTC was an independent prognostic marker for progression-free survival, whereas PSA and alkaline phosphatase serum levels, Gleason score, or T-stage were not. EGFR-positive patients had significantly shorter time to progression (5 months) compared to EGFR-negative patients (11 months) (P < 0.05).

CONCLUSIONS: In this explorative study, CTCs were detected in 98% of M1 patients and detection of EGFR in CTCs was strongly associated with poor outcome, which indicated that phenotypical analysis of CTC could be a promising prognostic marker of ADT-response in castration-naïve metastatic PC patients. Prostate 77:849-858, 2017. © 2017 Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2017
Keywords
CTC, androgen deprivation therapy, epidermal growth factor receptor
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-159987 (URN)10.1002/pros.23325 (DOI)000399884100004 ()28295408 (PubMedID)
Funder
Swedish Cancer SocietySwedish Foundation for Strategic Research
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-13Bibliographically approved
Anand, A., Morris, M. J., Larson, S. M., Minarik, D., Josefsson, A., Helgstrand, J. T., . . . Bjartell, A. (2016). Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide. EJNMMI Research, 6, Article ID 23.
Open this publication in new window or tab >>Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide
Show others...
2016 (English)In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 6, article id 23Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.

METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall's tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.

RESULTS: Eighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = -0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.

CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.

Place, publisher, year, edition, pages
Springer, 2016
Keywords
Bone Scan Index (BSI), Bone scan, Enzalutamide, Imaging biomarker, Metastatic castration-resistant prostate cancer (mCRPC)
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-159986 (URN)10.1186/s13550-016-0173-z (DOI)000371715100002 ()26960325 (PubMedID)
Funder
Swedish Cancer Society, 140274
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-13Bibliographically approved
Tidehag, V., Hammarsten, P., Egevad, L., Grantors, T., Stattin, P., Leanderson, T., . . . Bergh, A. (2014). High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome. European Journal of Cancer, 50(10), 1829-1835
Open this publication in new window or tab >>High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome
Show others...
2014 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 10, p. 1829-1835Article in journal (Refereed) Published
Abstract [en]

Purpose: To elucidate if the density of inflammatory cells expressing S100A9 in malignant and surrounding non-malignant prostate tissues is a prognostic marker for outcome in prostate cancer patients. Experimental design: Tissue was obtained from 358 men diagnosed with prostate cancer at transurethral resection of the prostate due to obstructive voiding problems, of which 260 were then followed with watchful waiting. Tissue microarrays of both malignant and non-malignant tissues were stained with an antibody against S100A9. The number of stained inflammatory cells was scored and related to clinical outcome and histopathological parameters of known prognostic value. Results: A high number of inflammatory cells expressing S100A9 in both malignant and surrounding non-malignant tissues were associated with significantly shorter cancer-specific survival. This association remained significant when Gleason score and local tumour stage were analysed together with S100A9 in a Cox regression model. Low number of S100A9 positive cells in non-malignant stroma was correlated to significantly longer cancer-specific survival also in patients with Gleason score 8-10 tumours. S100A9 positive cells in tumour stroma were correlated with Gleason score, hyaluronan, platelet-derived growth factor receptor beta (PDGFR-beta), and androgen receptor (inverse correlation) in tumour stroma. S100A9 positive cells in non-malignant stroma correlated with androgen receptor in this tissue compartment (inverse correlation). Conclusions: A high number of S100A9 positive inflammatory cells in tumour stroma and in non-malignant stroma were associated with shorter cancer-specific survival in prostate cancer patients.

Keywords
Prostate cancer, S100A9, Prognostic marker, Watchful waiting
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-91261 (URN)10.1016/j.ejca.2014.03.278 (DOI)000337875800016 ()
Available from: 2014-07-30 Created: 2014-07-28 Last updated: 2018-06-07Bibliographically approved
Mirtti, T., Leiby, B. E., Abdulghani, J., Aaltonen, E., Pavela, M., Mamtani, A., . . . Nevalainen, M. T. (2013). Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy. Human Pathology, 44(3), 310-319
Open this publication in new window or tab >>Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy
Show others...
2013 (English)In: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 44, no 3, p. 310-319Article in journal (Refereed) Published
Abstract [en]

There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. Most PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death. In preclinical PCa models, Stat5a/b promotes PCa growth and progression. Stat5a/b is critical for PCa cell viability in vitro and for tumor growth in vivo and promotes metastatic dissemination of cancer in nude mice. Here, we analyzed the predictive value of high nuclear Stat5a/b protein levels in 2 cohorts of PCas: Material I (n = 562) PCas treated by radical prostatectomy (RP), and Material II (n = 106) PCas treated by deferred palliative therapy. In intermediate GS PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariable analysis; P < .0001, multivariable analysis; HR = 1.82, P = .017) and early PCa-specific death (univariable analysis; P = .028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariable (P < .0001) and multivariable (HR = 1.61; P = .012) analysis in the entire cohort of patients treated by RP regardless of the GS. Patients treated by deferred palliative therapy, elevated nuclear Stat5a/b expression was associated with early PCa-specific death by univariable Cox regression analysis (HR. = 1.59; 95% CI = [1.04, 2.44]; P = .034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after RP for intermediate GS PCas. (c) 2013 Elsevier Inc. All rights reserved.

Keywords
Stat5a/b, Prostate cancer, Recurrence, Prostate cancer-specific death, Therapy failure
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-67579 (URN)10.1016/j.humpath.2012.06.001 (DOI)000315126300002 ()
Available from: 2013-06-04 Created: 2013-03-25 Last updated: 2018-06-08Bibliographically approved
Fowler, C. J., Josefsson, A., Thors, L., Chung, S. C., Hammarsten, P., Wikström, P. & Bergh, A. (2013). Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1831(10), 1579-1587
Open this publication in new window or tab >>Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer
Show others...
2013 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1831, no 10, p. 1579-1587Article in journal (Refereed) Published
Abstract [en]

Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide. Here we have investigated whether the expression levels of FAAH and CB1 receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB1 receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB1IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB1IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB1IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15 year of disease-specific survival (%) of 68 +/- 7 (low endoglin, low FAAH), 45 +/- 11 (high endoglin, low FAAH), 77 +/- 6 (low endoglin, high FAAH) and 21 +/- 10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a-1b relative to stages 2-4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.

Keywords
Cannabinoid CB1 receptor, Fatty acid amide hydrolase, Angiogenesis, Endoglin, von Willebrand factor, Prostate cancer
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-81827 (URN)10.1016/j.bbalip.2012.12.005 (DOI)000324719700010 ()
Available from: 2013-10-24 Created: 2013-10-22 Last updated: 2018-06-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2013-0887

Search in DiVA

Show all publications