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- Andrén, Ove, 1963-
(författare)
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Natural history and prognostic factors in localized prostate cancer
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects. The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden. Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer. The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment. Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.
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- Fiorentino, M., et al.
(författare)
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Immunohistochemical Expression of BRCA1 in Prostate Cancer
- 2009
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Ingår i: Laboratory Investigation. - : Nature Publishing Group. - 0023-6837 .- 1530-0307. ; 22, s. 169A-169A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: BRCA1 is a multifunctional protein involved in DNA repair, gene transcription and the regulation of cell-cycle check-points. While germline mutations of BRCA1 are rare in prostate cancer and seem to play a limited role in tumor susceptibility, BRCA1 expression has not been investigated to date.Design: We analyzed the immunohistochemical expression of BRCA1 in paraffin embedded samples from 524 men with prostate cancer belonging to the Physicians’ Health Study and the Swedish Watchful Waiting cohorts of prostate cancer patients. High density tissue micro-arrays (TMA) including at least three tumor cores for each case were utilized for the immunohistochemical staining with the monoclonal MS110 antibody specific for the N-terminus of the 220 kDa BRCA1 protein. Cases were scored as negative or positive for BRCA1 immunostaining. The Ki67 proliferation index was also assessed on the same TMAs and evaluated by quantitative image analysis.Results: A positive nuclear immunostaining for BRCA1 was revealed in 62 of 524 (11.9%) patients while normal prostate control cores were all negative. BRCA1 positive tumors were associated with 4 times greater proliferation rate compared to BRCA1 negative tumors (p ∼ 0.0003). In addition, we found a linear trend such that tumors with greater number of TMA cores expressing BRCA1 had stronger extent of proliferation. Men with BRCA1 positive tumors had a slightly higher Gleason’s score (mean 7.5) compared to those negative for BRCA1 (mean 7) No significant correlation was found between BRCA1 staining and cancer-specific death.Conclusions: BRCA1 protein is expressed in a small subset of prostate cancers characterized by high proliferation index but not in normal prostate tissue. Expression of BRCA1 might be acquired in selected tumors to prevent DNA damage in actively replicating cells. A different role independent of germline mutations might be disclosed for BRCA1 as cell cycle regulator in prostate cancer.
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- Jerlström, Tomas, 1969-
(författare)
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Clinical aspects of cystectomy and urinary diversion
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore different aspects of treatment of advanced urinary bladder cancer with radical cystectomy, pelvic lymph node dissection, and urinary diversion. Surgery that carry a high risk of complications as well as mortality. Aside from complications and risk of recurrance, patients have to cope with lifelong postoperative changes of body function, including sexual function, and body image, all affecting quality of life (QoL). The thesis comprises four papers. In the first paper, we compared functional outcome and QoL following two types of ileal orthotopic neobladder substitution. The results suggest that the S-shaped substitute entails better functional results than the U-shaped substitute, with better continence, especially at night. There was no difference in QoL. The second paper reports results from the first year of registration in the nation-wide Swedish Cystectomy Register. Analysis of risk factors for complications showed that high age and prolonged operation are associated with increased risk of short-term complications. The third paper investigated whether preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC) affects the risk of shortterm complications after radical cystectomy, using data from the Cystectomy Register covering 1340 patients of whom 39 percent received preoperativevchemotherapy. We found no such increase in risk. In the fourth paper, we analysed the results of a validation study of the Cystectomy Register. The validation showed 17 percent more low grade complications, three percent more high grade complications, and five percent more readmissions, within 90 days of surgery. Hence, a third-party validation may improve the validity of the register
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- Offermann, Anne, et al.
(författare)
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TRIM24 as Independent Prognostic Marker in Prostate Cancer
- 2018
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 31:Suppl. 2, s. 372-373
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Simply applicable biomarkers for prostate cancer (PCa) predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen-receptor signaling and to correlate with poor outcome. Based on these data, we validated TRIM24 as a prognostic biomarker for PCa.Design: We performed TRIM24 immunohistochemistry on two independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases and 129 benign prostatic samples from 497 patients. Expression data were correlated with clinic-pathological data including biochemical recurrence free survival (bRFS) as endpoint.Results: Benign samples show no/low TRIM24 expression in 94%, while tumors demonstrate significantly higher levels. Strongest expression is observed in metastatic tumors. In multivariate analyses, TRIM24 up-regulation correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher Grade Group, positive nodal status and extraprostatic tumor growth.Conclusions: Using two large independent cohorts, we found that TRIM24 expression predicts patients’ risk to develop disease recurrence with high accuracy and independently from other established prognostic markers. To our knowledge, TRIM24 is the first prognostic biomarker to be independent, accurate and reproducible on three different primary PCa cohorts. Thus, we strongly suggest introducing TRIM24 in clinical routine as a simple immunohistochemical test.
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