| 1. |
- Bratt, Ola, 1963, et al.
(författare)
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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)
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 76:4, s. 461-466
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Tidskriftsartikel (refereegranskat)abstract
- 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 40-75 yr, 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/cm(3) 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. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Hammarsten, Peter, et al.
(författare)
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Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome
- 2019
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 32, s. 1310-1319
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Tidskriftsartikel (refereegranskat)abstract
- Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975–1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts. © 2019, The Author(s).
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| 3. |
- Hägglöf, Christina, et al.
(författare)
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TMPRSS2-ERG Expression Predicts Prostate Cancer Survival and Associates with Stromal Biomarkers
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFR beta and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.
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| 4. |
- Jakobsen, Lasse H., et al.
(författare)
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Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy : an international study of 264 real-world patients
- 2020
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 189:4, s. 661-671
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Tidskriftsartikel (refereegranskat)abstract
- Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47 years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12 months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: −0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.
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| 5. |
- Thomasson, Marcus, et al.
(författare)
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LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer
- 2011
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:12, s. 2843-2852
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Tidskriftsartikel (refereegranskat)abstract
- The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T-stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer-specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances.
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