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| 2. |
- Boman, Kurt, et al.
(författare)
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Healthcare resource utilization associated with heart failure with preserved versus reduced ejection fraction : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 346-346
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from two Swedish counties.Methods: Patients with HF were identified via electronic medical records (EMRs) from primary and/or secondary care in Uppsala and Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify HFpEF (defined as ejection fraction ≥50%) and HFrEF (defined as <50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. Patients were followed from date of first diagnosis (index date) to end of study period or EMR collection, date of death or loss to follow-up for other reasons, whichever came first. Unadjusted all-cause and cardiovascular disease (CVD)-related hospitalization rates were assessed using a Cox proportional hazards model, accounting for age, sex, setting of first diagnosis (primary vs secondary care), HF phenotype and NT-proBNP level.Results: In total, 8702 patients with HF were identified. HF phenotype was known in 3167 patients; 64.6% had HFrEF, 35.4% had HFpEF. Patients with HFrEF were younger (mean±SD: 69.9±13.7 vs 74.2±12.6 years) with a lower Charlson comorbidity index (1.65 vs 1.83) than those with HFpEF. All-cause hospitalization rates were marginally lower for HFrEF than for HFpEF (mean [95% CI] proportion of patients hospitalized within 1 year of diagnosis, 72.5 [70.1–74.8]% vs 73.8 [70.7–77.0]%; hazard ratio [HR] over whole follow-up period, 0.87 [0.79–0.97], p=0.0093). The proportion of patients hospitalized was higher for those diagnosed in secondary care than in primary care, particularly within 1 year of diagnosis (1-year rate, 69.6 [68.3–71.0]% vs 59.1 [56.8–61.4]%; HR, 1.15 [1.07–1.23], p=0.0002). Similar trends were observed for CVD-related hospitalization rates for HFrEF vs HFpEF (1-year rate, 69.5 [67.1–71.9]% vs 70.7 [67.5–74.0]%; HR, 0.89 [0.81–0.99], p=0.0309) and for patients diagnosed in secondary vs primary care (1-year rate, 66.6 [65.3–68.0]% vs 56.2 [53.8–58.5]%; HR, 1.15 [1.07–1.24], p=0.0001). Numbers of hospitalizations and outpatient visits decreased with time after diagnosis for HFrEF, but increased slightly for HFpEF after 2 years (Figure). The mean±SD total number of all-cause days of hospitalization during the first year after diagnosis was lower in patients with HFrEF vs HFpEF (19.9±26.1 vs 26.3±34.5 days), while the number of HF-related days of hospitalization was similar (16.0±22.4 vs 17.2±24.0 days).Conclusions: Number and duration of hospital stays were significantly lower over time in patients with HFrEF than HFpEF; this may be explained by the comorbidity burden in the latter group.
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| 5. |
- Olofsson, Mona, et al.
(författare)
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A description of characteristics of very elderly patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 362-362
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Over a quarter of patients with heart failure (HF) in Sweden are very elderly (defined as aged ≥85 years). Evidence on the demographic and clinical characteristics of these patients, and on the diagnostic procedures they receive in clinical practice, is scarce.Methods: Patients with HF were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify patients with HF with preserved (HFpEF, ≥50%) and reduced (HFrEF, <50%) ejection fraction. Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was the index date. ICD-10 codes were also used to identify comorbidities. A 10-year look-back period was used to exclude prevalent HF cases. Patient characteristics were assessed at index, except comorbidities (in the 5 years before index) and pre-diagnosis comedications (in the first year before index).Results: In total, 8702 patients with HF were identified; 27.7% were aged ≥85 years. Compared with patients <85 years, more patients ≥85 years were female (60.2% vs 40.6%) and fewer were overweight (BMI >25 kg/m2, 42.3% vs 63.5%). In both groups, HF was more commonly diagnosed in secondary than in primary care, but patients ≥85 years were more often diagnosed in primary care than those <85 years (31.2% vs 20.9%). Fewer patients ≥85 years than those <85 years received an echocardiogram at diagnosis (19.3% vs 42.9%); of those who did, more patients ≥85 years than <85 years had HFpEF (46.8% vs 33.4%). Patients ≥85 years had a comorbidity burden similar to those <85 years (mean number of comorbidities/patient, 2.4 vs 2.3); prevalence of atrial fibrillation (32.0% vs 30.4%), hypertension (53.2% vs 53.0%) and ischaemic heart disease (20.5% vs 22.5%) were also similar in both age groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and systolic blood pressure (BP) increased with age, and diastolic BP and estimated glomerular filtration rate decreased. Potassium and sodium levels did not differ between age groups (Table). The most common pre-diagnosis comedications were ?-blockers, antithrombotic agents and diuretics; ?-blockers were less frequently prescribed in patients ≥85 years (59.6% vs 64.4%), and antithrombotic agents and diuretics were more frequently prescribed in those ≥85 years (antithrombotic agents, 57.0% vs 54.3%; diuretics, 50.1% vs 43.1%).Conclusions: Very elderly patients with HF in Sweden are clinically different from younger patients, with a higher prevalence of HFpEF and higher NT-proBNP levels (as expected). Most importantly, very elderly patients seldom receive an echocardiogram at diagnosis.
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| 12. |
- Wikstrom, G., et al.
(författare)
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Drug treatment patterns in patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 55-55
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Limited data are available on longitudinal drug treatment patterns in newly diagnosed patients with heart failure (HF) with preserved (HFpEF), reduced (HFrEF) and unknown ejection fraction (EF) in Sweden. We evaluated drug treatment patterns in these patients based on ESC 2012 guidelines, which recommend treatment with angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), ?-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs) for HFrEF (ESC does not make recommendations for HFpEF or unknown EF).Methods: Patients were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data identified HFrEF (<50%) and HFpEF (≥50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was defined as the index date. A 10-year look-back period was used to exclude prevalent HF cases. ATC codes were identified from drug prescriptions. Patients with a 4-year look-back and 2 years of follow-up were included.Results: Overall, 4357 patients were included (mean± SD age, 76.6± 12.6 years; 27.7% aged ≥85 years; HFrEF, 24.6%; HFpEF, 12.9%; unknown EF, 62.5%). At the index date, 63.0% of patients were treated with an ACEi or an ARB, 62.3% with a BB and 16.0% with an MRA; 18.5% were not receiving treatment. The most common treatment groups (monotherapy or combinations) were: ACEi + BB (HFrEF, 20.5%; HFpEF, 21.0%; unknown EF, 23.5%); BB monotherapy (HFrEF, 12.1%; HFpEF, 14.0%; unknown EF, 15.6%); and ARB + BB (HFrEF, 8.5%; HFpEF, 12.3%; unknown EF, 12.3%) (Figure). The majority of patients receiving an ACEi or ARB at the index date continued to do so for the following 2 years (ACEi, 63.6%; ARB, 60.9%); most of these were receiving doses lower than those recommended by the ESC (70.8% and 88.9%, respectively). A small proportion of patients receiving an ACEi at the index date switched to an ARB over the 2-year period (4.1%) and vice versa (2.6%). Most patients were not receiving the recommended ESC dose before switching (ACEi, 81.8%; ARB, 77.8%). Similarly, most patients who discontinued an ACEi (37.3%) or ARB (39.1%) were not receiving the recommended dose before discontinuation (ACEi, 64.8%; ARB, 87.4%).Conclusions: A large proportion of patients with HF in Sweden do not receive drug combinations recommended by the ESC. Furthermore, few patients are prescribed ESC-recommended doses of HF drugs and few undergo up-titration of treatment before switching. These findings are remarkable for HFrEF, for which guidelines are established. These findings may be partly reflective of the high proportion of elderly patients studied.
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| 14. |
- Blixt, Maria, et al.
(författare)
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MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma
- 2022
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.
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| 15. |
- Fili, M, et al.
(författare)
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Effect of plaque brachytherapy dose and dose rate on risk for disease-related mortality in 1238 patients with choroidal melanoma
- 2021
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Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- Episcleral brachytherapy is the most common treatment for medium-sized choroidal melanomas. Although controversial, inadequate brachytherapy dose and dose rates have at least a hypothetical implication on patient survival.MethodsAll patients who received ruthenium-106 or iodine-125 brachytherapy for choroidal melanoma at St. Erik Eye Hospital 1996 to 2016 were included (n=1238). Cox regression hazard ratios for melanoma-related mortality across deciles, quartiles and individual integers of apex radiation doses (Gy) and dose rates (Gy/hour) were calculated, adjusted for tumour size and location.ResultsThe average radiation dose at the tumour apex ranged from 73.0 Gy in the first decile to 108.6 Gy in the tenth. Decreasing apex dose by 1 Gy increments or by decile or quartile group was not associated with melanoma-related mortality (p>0.2) The average radiation dose rate at the tumour apex ranged from 0.5 Gy/hour in the first decile to 2.8 Gy/hour in the tenth. Similarly, decreasing apex dose rate by 1 Gy/hour increments or by decile or quartile groups was not associated with melanoma-related mortality (p>0.5).ConclusionThere are no increased hazards for choroidal melanoma-related mortality after brachytherapy with decreasing doses between 108.6 and 73.0 Gy, or with decreasing dose rates between 2.8 and 0.5 Gy/hour.
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| 19. |
- Fili, M, et al.
(författare)
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Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of ≥5.5 mm
- 2020
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Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 104:1, s. 26-32
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Tidskriftsartikel (refereegranskat)abstract
- Episcleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and β-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (<6 mm). In this study, we compare ocular and patient survival in thicker tumours treated with the respective radioisotope.MethodsAll patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups.Results317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p<0.001). Size-controlled Cox regression HRs for postbrachytherapy enucleation (125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5–7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%).ConclusionsRates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.
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| 24. |
- Gill, V, et al.
(författare)
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Trends in Uveal Melanoma Presentation and Survival During Five Decades: A Nationwide Survey of 3898 Swedish Patients
- 2022
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Ingår i: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 9, s. 926034-
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to most other cancers, uveal melanoma (UM) is characterized by an absence of major improvements in patient survival during the last several decades. In this study, we examine changes in incidence rates, patient age and tumor size at diagnosis, treatment practices and survival for patients diagnosed in Sweden during the period 1960–2010.MethodsAll patients diagnosed with posterior UM between January 1st, 1960, and December 31st, 2009, in Sweden, were included (n = 3898). Trends in incidence, primary treatment modality, patient age and tumor size were analyzed. Disease-specific survival was plotted in Kaplan–Meier curves and the cumulative incidence of UM-related mortality was evaluated in competing risk analysis.ResultsCrude (6.5–11.6 cases/million/year) and age-standardized incidence rates (5.6–9.6 cases/million/year) varied between individual years during the study period, but both had a stable linear trend overall (p ≥ 0.12). Gradually, plaque brachytherapy with ruthenium-106 replaced enucleation as the most common primary treatment. The mean patient age at diagnosis increased from 59.8 years in 1960 to 66.0 in 2009. Conversely, the mean tumor size became gradually smaller during the period. In linear regression, the basal diameter and tumor apical thickness decreased with a slope coefficient of −0.03 mm (p = 0.012) and −0.05 mm (p = 1.2 × 10–5) per year after 1960, respectively. Patients diagnosed after 1990 had significantly better disease-specific survival than patients diagnosed before 1990 (p = 2.0 × 10–17). Similarly, the cumulative incidence of UM-related mortality was highest for patients diagnosed 1960–1969 and 1970–1979, with slightly lower incidences for patients diagnosed 1980–1989 and even lower for those diagnosed after 1990 (p = 7.1 × 10–13). The incidence of mortality from other causes than UM did not differ between periods (p = 0.16).ConclusionIn the period from 1960–2010, crude and age-standardized incidence rates of UM have remained stable in Sweden. Several other aspects have changed: Plaque brachytherapy with ruthenium-106 has replaced enucleation as the most common primary treatment modality; patients have become older and their tumors smaller at the time of diagnosis; and their survival has improved. This might indicate a beneficial survival effect of earlier diagnosis and treatment, but the potential influence from lead-time bias should be taken into consideration.
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| 32. |
- Robertson, S, et al.
(författare)
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Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer
- 2018
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Ingår i: Journal of clinical pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 71:9, s. 787-794
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Tidskriftsartikel (refereegranskat)abstract
- The accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome.MethodsTwo retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.ResultsIn both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis.ConclusionsThis study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes.
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| 44. |
- Stalhammar, G
(författare)
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Forty-year prognosis after plaque brachytherapy of uveal melanoma
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 11297-
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the long-term patient survival after plaque brachytherapy of uveal melanoma is examined. All patients treated between 1980 and 1999 at a single institution were included (n = 677). 533 (79%) had deceased before the end of follow-up. The median follow-up for the 144 survivors was 25.4 years (SD 5.2). Uveal melanoma-related mortality was 18% by 5 years, 28% by 10 years, 32% by 15 years, 35% by 20 years, and 36% by 25 to 40 years. 172 of 209 (82%) uveal melanoma-related deaths occurred within the first decade after brachytherapy. Relative survival rates were 74% at 5 years, 64% at 10 years, 62% at 20 years, 83% at 30 years and ≥100% at 32 to 40 years. Tumor diameter and local recurrence were independent predictors of uveal melanoma-related mortality in multivariate Cox proportional hazards analysis. In conclusion, uveal melanoma has a high mortality rate and most uveal melanoma-related deaths occur in the first decade after treatment. Long-term survivors may have a survival advantage to individuals of the same sex and age from the general population.
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| 45. |
- Stalhammar, G, et al.
(författare)
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Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Malignant tumors are rarely homogenous on the morphological, genome, transcriptome or proteome level. In this study, we investigate the intratumor heterogeneity of BAP-1 expression in uveal melanoma with digital image analysis of 40 tumors. The proportion of BAP-1 positive cells was measured in full tumor sections, hot spots, cold spots and in scleral margins. The mean difference between hot spots and cold spots was 41 percentage points (pp, SD 29). Tumors with gene expression class 1 (associated with low metastatic risk) and 2 (high metastatic risk) had similar intratumor heterogeneity. Similarly, the level of intratumor heterogeneity was comparable in tumors from patients that later developed metastases as in patients that did not. BAP-1 measured in any tumor region added significant prognostic information to both American Joint Committee on Cancer (AJCC) tumor size category (p ≤ 0.001) and gene expression class (p ≤ 0.04). We conclude that there is substantial intratumor heterogeneity in uveal melanoma BAP-1 expression. However, it is of limited prognostic importance. Regardless of region, analysis of BAP-1 expression adds significant prognostic information beyond tumor size and gene expression class.
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