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- Adamo, Hanibal Hani, 1984-, et al.
(författare)
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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
- 2019
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Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 79:5, s. 435-445
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Tidskriftsartikel (refereegranskat)abstract
- Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.
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| 2. |
- Adamo, Hanibal, et al.
(författare)
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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome.
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| 3. |
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| 4. |
- Bovinder Ylitalo, Erik, et al.
(författare)
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Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:5, s. 776-787
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Tidskriftsartikel (refereegranskat)abstract
- Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy.Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-naïve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription–polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non–AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non–AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.
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| 5. |
- Bratt, Ola, et al.
(författare)
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Upper limit of cancer extent on biopsy defining very low-risk prostate cancer
- 2015
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:2, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. Patients and Methods We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern <= 3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. Results In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and < 8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). Conclusions Men aged < 70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is < 8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.
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| 6. |
- Carlsson, Stefan, et al.
(författare)
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Current routines for transrectal ultrasound-guided prostate biopsy: A web-based survey by the Swedish Urology Network
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 46:6, s. 405-410
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study aimed to survey current Swedish practices for performing and handling transrectal ultrasound-guided prostate biopsies. Material and methods. A Swedish Urology Network (SUNe) was organized for the distribution of information, survey studies and research collaborations. A web-based questionnaire was distributed to the members in 2011. Results. In this first SUNe survey, 137 (91%) of the 151 members replied. All used antibiotic prophylaxis (84% ciprofloxacin, 12% trimethoprim-sulfamethoxazole), most commonly (63%) as a single dose of ciprofloxacin. Local anaesthesia was used by 87%. Half of the respondents only used a "side-fire" probe, whereas 17% always used an "end-fire" probe. Most (84%) routinely took 10 or more biopsy cores. About three-quarters started with the right base of the prostate and did not routinely take midline biopsies. More than one-third never or rarely sampled the anterior part of the prostate. There was great variability in how biopsy location was reported, but 71% considered a national standardized coordinate system desirable. Fine-needle aspiration was used occasionally by 39%, in more than 10% of cases by 6% and always by 2%. Most urologists mounted the biopsy cores on paper before fixation (78%), put only one core per jar (75%) and used flat-bottomed jars (70%). Conclusions. Most routines for handling of prostate biopsies, antibiotic prophylaxis, local anaesthesia and number of cores were uniform. However, there is still a need for standardization of the performance of ultrasound-guided biopsies. Although the method used to specify biopsy location varied greatly, most urologists would prefer a national standardized system.
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| 7. |
- Chung, Sui Chu, et al.
(författare)
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A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:1, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- In the light of findings indicating that cannabinoids can affect the proliferation of a number of cancer cell types and that cannabinoid receptor expression is higher in prostate cancer cell lines than in non-malignant cells, we investigated whether the level of cannabinoid 1 receptor immunoreactivity (CB(1)IR) in prostate cancer tissues is associated with disease severity and outcome. Formalin-fixed paraffin-embedded non-malignant and tumour tissue samples from patients who were diagnosed with prostate cancer at a transurethral resection for voiding problems were used. CB(1)IR, which was scored in a total of 399 cases, was associated with the epithelial cell membranes, with little staining in the stroma. Patients with a tumour CB(1)IR score greater or equal to the median (2) had a significantly higher proportion of Gleason scores 8-10, metastases at diagnosis, tumour size and rate of cell proliferation at diagnosis than patients with a score<2. For 269 cases, tumour CB(1)IR was measured for patients who only received palliative therapy at the end stages of the disease, allowing the influence of CB(1)IR upon the disease outcome to be determined. Receiver operating characteristic (ROC) curves showed an area under the curve of 0.67 (95% confidence limits 0.59-0.74) for CB(1)IR in the tumour. CB(1)IR in non-malignant tissue was not associated with disease outcome. A tumour CB(1)IR score >or=2 was associated with a significantly lower disease specific survival. A Cox proportional hazards regression indicated that the tumour CB(1)IR score and the Gleason score were independent prognostic variables. It is concluded that a high tumour CB(1)IR score is associated with prostate cancer severity and outcome.
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| 8. |
- Danneman, Daniela, et al.
(författare)
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Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens : nationwide trends 2000-2012
- 2017
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 119:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).
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| 9. |
- Danneman, Daniela, et al.
(författare)
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Gleason inflation 1998-2011 : a registry study of 97 168 men
- 2015
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Ingår i: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 115:2, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer. Patients and Methods: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed. Results: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned. Conclusions: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.
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