| 1. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma
- 2020
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Ingår i: Applied immunohistochemistry & molecular morphology (Print). - : Lippincott Williams & Wilkins. - 1541-2016 .- 1533-4058. ; 28:3, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.
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| 2. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Quantity and quality of nucleic acids extracted from archival formalin fixed paraffin embedded prostate biopsies
- 2018
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.METHODS: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.RESULTS: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.CONCLUSIONS: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.
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| 3. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma
- 2019
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:5, s. 4566-4574
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most commonly diagnosed renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk of recurrence at an early stage of disease may improve patient outcome. The factors presently used in a clinical setting cannot reliably predict the natural history of the disease. Therefore, there is a requirement to identify novel biomarkers that can aid in predicting patient outcome. Previous studies have indicated that microRNAs (miRNAs/miRs) are potential candidates as prognostic biomarkers for patients suffering from RCC. Consequently, the aims of the present study were to validate the potential of 3 of these miRNAs to predict the prognosis of patients with RCC, and to investigate the stability of endogenous control genes for miRNA studies in RCC tissues. The expression of 7 endogenous controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in formalin-fixed paraffin-embedded tumor and benign tissues from patients suffering from clear cell RCC (ccRCC). The analyses identified RNU48 and U47 as the most stable endogenous controls. The expression of miR-126, miR-21 and miR-10b was analyzed using RT-qPCR in renal tissues from 116 patients diagnosed with ccRCC. All three investigated miRNAs were differentially expressed between malignant and benign tissues. miR-126 and miR-10b were also differentially expressed between grades and stages of ccRCC. In a univariate, but not in a multivariate model, low expression of miR-126 was associated with shorter time to recurrence of the disease. The results of the present study indicate that of the 3 miRNAs investigated, the expression of miR-126 has the strongest potential as a prognostic biomarker for patients suffering from ccRCC.
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| 4. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer
- 2018
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Ingår i: The Prostate. - Hoboken, USA : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 78:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs ). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.METHODS: Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.RESULTS: In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart.CONCLUSIONS: Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established.
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| 5. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
- 2020
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome. Background: It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective: To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants: A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis: Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations: We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions: Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary: The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.
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| 6. |
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| 7. |
- Davidsson, Sabina, et al.
(författare)
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PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes
- 2019
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 2:2, s. 214-221
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity.Objective: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer.Design, setting, and participants: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry.Outcome measurements and statistical analysis: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.Results and limitations: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1–positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation.Conclusions: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes.Patient summary: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.
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| 8. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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The presence of PD-L1 in men with localized prostate cancer
- 2017
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Ingår i: Medical research archives. - Walnut CA, USA : KEI Journals. - 2375-1916 .- 2375-1924. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent therapeutic strategies for different cancer types have focused on targeting immune check-points, such as programmed death-1 (PD-1) and its ligand PD-L1. However, it was recently reported that men with castration-resistant prostate cancer did not respond to PD-1 blockade as monotherapy. The unresponsiveness could potentially be explained by low expression of PD-L1 on prostate tumor cells. This study investigated the expression of PD-L1 on tumor cells and tumor infiltrating lymphocytes (TILs) in men with primary prostate cancer.Material and Methods: Immunohistochemical analysis of PD-L1 expression was performed in a cohort of men undergoing transurethral resection of the prostate and diagnosed with prostate cancer. The expression was evaluated in tissue microarrays from 522 patients with at least 25 years of follow-up.Results: Only four of the 522 evaluated cases were positive for PD-L1, positivity on tumor cells were found in three of the cases, of which one case also had positivity on TILs, while a fourth case only had positivity on TILs.Conclusion: Our data suggest that treatments targeting the PD-1/PD-L1 interaction may not be successful as monotherapy in patients diagnosed with localized prostate cancer due to low expression of PD-L1.
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| 9. |
- Dorofte, Luiza, 1982-, et al.
(författare)
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Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care
- 2022
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Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 480:4, s. 879-886
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors.
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| 10. |
- Grabowska, Beata, et al.
(författare)
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Clinical outcome and time trends of surgically treated renal cell carcinoma between 1986 and 2010 : results from a single centre in Sweden
- 2018
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis Group. - 2168-1805 .- 2168-1813. ; 52:3, s. 206-212
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aims of this study were to create a cohort of retrospectively collected renal cell carcinoma (RCC) specimens to be used a basis for prognostic molecular studies, and to investigate the outcome and time trends in patients surgically treated for RCC in a single-centre cohort.MATERIALS AND METHODS: Patients undergoing surgery for RCC between 1986 and 2010 were included in the study. Medical records were reviewed, and the diagnostic tissue was re-evaluated according to a modern classification. The change in patient and tumour characteristics over time was analysed.RESULTS: The study included 345 patients. Smaller tumours, as indicated by primary tumour diameter, tumour (T) stage and American Joint Committee on Cancer (AJCC) stage, were found more frequently in later years compared to the early 1990s. No changes in the clinical outcome for the patients were seen among the time periods investigated. Increasing T stage, AJCC stage, primary tumour diameter and decreasing haemoglobin levels were associated with cancer-specific mortality in univariate analysis. A high calcium level was significantly associated with increased cancer-specific mortality (hazard ratio = 4.25, 95% confidence interval 1.36-13.28) in multivariate analysis.CONCLUSIONS: This study on patients who underwent surgery for RCC from 1986 to 2010 at a single institution in Sweden indicates that there has been a change in tumour characteristics of patients diagnosed with RCC over time. It was also shown that calcium levels were an independent prognostic factor for cancer-specific mortality in this cohort. This cohort could provide a valuable basis for further molecular studies.
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| 11. |
- Ricci, Costantino, et al.
(författare)
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HPV Status and World Health Organization 2016 Classification of Penile Squamous Cell Carcinoma and Penile Intraepithelial Neoplasia : 206 Cases from a Single, Contemporary, Western Cohort of Patients with Emphasis on the "Discordant Cases"
- 2020
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 33:Suppl 2, s. 960-961
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Penile squamous cel carcinoma (pSCC) cancer has been considered a rare tumour in the western world. Although some conflicting results, the most recent meta-analyses report an increase in its incidence and in the percentage of HPV(+) cases in numerous western countries. This scenario mirrors what observed for HPV(+) oropharynx cancer and could be explained by changes in sexual practice and in exposure of men to HPV. In this study, we analyzed pathological features and HPV-DNA prevalence in a contemporary, western pSCC cohort.Design: This study enrolled 206 patients with pSCC from Örebro University. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA genotyping were performed using PCR method Anyplex II HPV28. In a subset of cases, HPV-DNA was also assessed in penile intraepithelial neoplasia (PeIN), lymph node metastasis (LnM) or both (51%, 11.6% and 18.9%). All the cases have been histologically re-classified according to the WHO 2016 classification of pSCC.Results: HPV -DNA was detected in 92/206 (44.7%) pSCC, 78/141 (55.3%) PeIN and 28/61 LnM (45.9%), respectively. HPV16 was the predominant type, representing 78.3% for pSCC, 79.5% for PeIN and 96.4% for LnM. In 7.8% of the cases, more than a HPV genotype has been detected in the same specimen or in different specimens of the same patients. Curiously, we found 8.5% of cases (14/164) with discordance of HPV-DNA detection in different specimens from the same patient (pSCC, PeIN and/or /LnM). In HPV(+) pSCC the predominant histologic subtype was “warty” (41.3%); in HPV(-) pSCC it was “usual” (65.8%). For PeIN, “warty” was the predominant subtype in HPV(+) PeIN (39.7%) and “differentiated” in HPV(-) PeIN (79.4%). For pSCC, we observed disagreement between histology and HPV status in 23.8% of cases: 13.1% HPV(+)/Non-HPV -related histology and 10.7% HPV(-)/HPV-related histology.Conclusions: HPV -DNA was observed in a relevant portion of pSCC and PeIN in our case series, confirming an increasing role of HPV in the pathogenesis of this disease. These results are particularly relevant, as they reflect the current epidemiological trend in the western world. Future studies are needed to clarify the exact role of HPV in cases with discordance between histology and HPV status and in cases with disagreement of HPV detection in different specimens from the same patient (pSCC, PeIN and/or LnM).
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| 12. |
- Tyekucheva, Svitlana, et al.
(författare)
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Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer
- 2017
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Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.Stromal cells contribute to tumor development but the mechanisms regulating this process are still unclear. Here the authors analyze gene expression profiles in the prostate and show that stromal gene signature changes ahead of the epithelial gene signature as prostate cancer initiates and progresses.
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| 13. |
- Zareba, Piotr, et al.
(författare)
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Perineural Invasion and Risk of Lethal Prostate Cancer
- 2017
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research Inc.. - 1055-9965 .- 1538-7755. ; 26:5, s. 719-726
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.Methods: We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.Results: The prevalence ofPNI was7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6; P < 0.001]. A positive, although not statistically significant, associationpersisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1; P = 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3; P = 0.04).Conclusions: These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness. Impact: Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis. (C) 2017 AACR.
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| 14. |
- Zelic, Renata, et al.
(författare)
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Estimation of Relative and Absolute Risks in a Competing-Risks Setting Using a Nested Case-Control Study Design : Example From the ProMort Study
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1165-1173
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.
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| 15. |
- Zelic, Renata, et al.
(författare)
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Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.
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| 16. |
- Zelic, Renata, et al.
(författare)
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Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade.
- 2022
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Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 14, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- Background: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear.Objective: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction.Patients and Methods: We conducted a case-control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998-2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC).Results: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS.Conclusion: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.
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| 17. |
- Zhang, Yiwen, et al.
(författare)
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A prospective study of intraprostatic inflammation, focal atrophy, and progression to lethal prostate cancer
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 28:12, s. 2047-2054
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance.METHODS: In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up.RESULTS: During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. Eighty-four percent of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR=0.45, 95% CI 0.30 to 0.69 for mild, HR=0.51, 95% CI 0.33 to 0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer.CONCLUSIONS: Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among prostate cancer patients.IMPACT: This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.
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