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Josefsson, Andreas
Publikasjoner (10 av 19) Visa alla publikasjoner
Josefsson, A., Damber, J.-E. & Welen, 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
Åpne denne publikasjonen i ny fane eller vindu >>AR-V7 expression in circulating tumor cells as a potential prognostic marker in metastatic hormone-sensitive prostate cancer
2019 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArtikkel i tidsskrift, Letter (Fagfellevurdert) Epub ahead of print
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.

sted, utgiver, år, opplag, sider
TAYLOR & FRANCIS LTD, 2019
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-162333 (URN)10.1080/0284186X.2019.1637540 (DOI)000478178600001 ()31286815 (PubMedID)
Tilgjengelig fra: 2019-08-16 Laget: 2019-08-16 Sist oppdatert: 2019-08-22
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
Åpne denne publikasjonen i ny fane eller vindu >>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)
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2019 (engelsk)Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 4, s. 461-466Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Elsevier, 2019
Emneord
Active surveillance, Biopsy, Prostate cancer, Randomised clinical trial
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-163538 (URN)10.1016/j.eururo.2019.02.035 (DOI)30878303 (PubMedID)2-s2.0-85062811212 (Scopus ID)
Tilgjengelig fra: 2019-09-25 Laget: 2019-09-25 Sist oppdatert: 2019-10-07bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>Circulating tumor cells mirror bone metastatic phenotype in prostate cancer
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2018 (engelsk)Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, nr 50, s. 29403-29413Artikkel i tidsskrift (Fagfellevurdert) 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.

Emneord
circulating tumor cells, liquid biopsies, skeletal metastases of prostate cancer
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-159988 (URN)10.18632/oncotarget.25634 (DOI)30034626 (PubMedID)
Tilgjengelig fra: 2019-06-11 Laget: 2019-06-11 Sist oppdatert: 2019-06-13bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naïve Prostate Cancer
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2017 (engelsk)Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, nr 8, s. 849-858Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Wiley-Blackwell, 2017
Emneord
CTC, androgen deprivation therapy, epidermal growth factor receptor
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-159987 (URN)10.1002/pros.23325 (DOI)000399884100004 ()28295408 (PubMedID)
Forskningsfinansiär
Swedish Cancer SocietySwedish Foundation for Strategic Research
Tilgjengelig fra: 2019-06-11 Laget: 2019-06-11 Sist oppdatert: 2019-06-13bibliografisk kontrollert
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.
Åpne denne publikasjonen i ny fane eller vindu >>Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide
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2016 (engelsk)Inngår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 6, artikkel-id 23Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Springer, 2016
Emneord
Bone Scan Index (BSI), Bone scan, Enzalutamide, Imaging biomarker, Metastatic castration-resistant prostate cancer (mCRPC)
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-159986 (URN)10.1186/s13550-016-0173-z (DOI)000371715100002 ()26960325 (PubMedID)
Forskningsfinansiär
Swedish Cancer Society, 140274
Tilgjengelig fra: 2019-06-11 Laget: 2019-06-11 Sist oppdatert: 2019-06-13bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome
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2014 (engelsk)Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, nr 10, s. 1829-1835Artikkel i tidsskrift (Fagfellevurdert) 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.

Emneord
Prostate cancer, S100A9, Prognostic marker, Watchful waiting
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-91261 (URN)10.1016/j.ejca.2014.03.278 (DOI)000337875800016 ()
Tilgjengelig fra: 2014-07-30 Laget: 2014-07-28 Sist oppdatert: 2018-06-07bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy
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2013 (engelsk)Inngår i: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 44, nr 3, s. 310-319Artikkel i tidsskrift (Fagfellevurdert) 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.

Emneord
Stat5a/b, Prostate cancer, Recurrence, Prostate cancer-specific death, Therapy failure
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-67579 (URN)10.1016/j.humpath.2012.06.001 (DOI)000315126300002 ()
Tilgjengelig fra: 2013-06-04 Laget: 2013-03-25 Sist oppdatert: 2018-06-08bibliografisk kontrollert
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
Åpne denne publikasjonen i ny fane eller vindu >>Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer
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2013 (engelsk)Inngår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1831, nr 10, s. 1579-1587Artikkel i tidsskrift (Fagfellevurdert) 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.

Emneord
Cannabinoid CB1 receptor, Fatty acid amide hydrolase, Angiogenesis, Endoglin, von Willebrand factor, Prostate cancer
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-81827 (URN)10.1016/j.bbalip.2012.12.005 (DOI)000324719700010 ()
Tilgjengelig fra: 2013-10-24 Laget: 2013-10-22 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Josefsson, A., Wikstrom, P., Egevad, L., Granfors, T., Karlberg, L., Stattin, P. & Bergh, A. (2012). Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance. Scandinavian Journal of Urology and Nephrology, 46(4), 247-257
Åpne denne publikasjonen i ny fane eller vindu >>Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance
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2012 (engelsk)Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 4, s. 247-257Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective: The aim of this study was to explore whether vascular density and tumour cell proliferation are related to the risk of prostate cancer death in patients managed by watchful waiting. Material and methods. From a consecutive series of men diagnosed with prostate cancer at transurethral resection in 1975-1990, tissue microarrays (TMAs) were constructed. A majority of men had no metastases at diagnosis and were followed by watchful waiting (n = 295). The TMAs were stained for Ki67, endoglin and factor VIII-related antigen (vWf).

Results: In univariate Cox analyses, increased Ki67 index, endoglin vascular density and vWf vascular density were associated with shorter cancer-specific survival. Ki67 index and endoglin vascular density added independent prognostic information to clinical stage, estimated tumour size and Gleason score (GS) in multivariate Cox analysis. In GS 6 tumours, high Ki67 index and high endoglin vascular density identified patients with poor outcome. After 15 years of follow-up not a single man out of 34 men with low staining for both markers (35% of all GS 6 tumours) had died of prostate cancer, in contrast to 15 prostate cancer deaths among the remaining 63 men with GS 6 tumours (65% cumulative risk of prostate cancer death). vWf vascular density in benign areas was a prognostic marker in GS 6 and 7 tumours.

Conclusions: Men with GS 6 tumours with both low Ki67 index and endoglin vascular density staining scores have a low risk of progression. Additional studies are needed to test whether these two markers can be applied to core biopsies to select patients suitable for surveillance.

sted, utgiver, år, opplag, sider
London: Informa Healthcare, 2012
Emneord
endoglin, Ki67, prostate cancer, prognostic markers, TINT, vWf
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-57815 (URN)10.3109/00365599.2012.669791 (DOI)000306479900002 ()
Tilgjengelig fra: 2012-08-17 Laget: 2012-08-16 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Hammarsten, P., Cipriano, M., Josefsson, A., Stattin, P., Egevad, L., Granfors, T. & Fowler, C. J. (2012). Phospho-Akt Immunoreactivity in Prostate Cancer: Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression. PLoS ONE, 7(10), e47994
Åpne denne publikasjonen i ny fane eller vindu >>Phospho-Akt Immunoreactivity in Prostate Cancer: Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression
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2012 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 10, s. e47994-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms. Methodology/Principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8-10, but not for patients with Gleason score 6-7. Conclusions/Significance: Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6-7.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-61971 (URN)10.1371/journal.pone.0047994 (DOI)000310261800027 ()
Tilgjengelig fra: 2012-12-18 Laget: 2012-12-04 Sist oppdatert: 2018-06-08bibliografisk kontrollert
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