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  • Borg, A, et al. (författare)
  • Prognostic significance of p53 overexpression in primary breast cancer : a novel luminometric immunoassay applicable on steroid receptor cytosols.
  • 1995
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 71:5, s. 1013-1017
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel quantitative luminometric immunoassay (LIA) has been developed for the measurement of wild-type and mutant p53 protein in extracts from breast tumour tissue. The LIA was found to yield reliable estimates of p53 expression in cytosol samples routinely prepared for steroid receptor analysis as compared with results obtained with immunohistochemical analysis. The LIA was evaluated on 205 primary breast tumour cytosols prepared for steroid receptor analysis and stored frozen at -80 degrees C for 6-8 years, p53 protein being detected in 65% of the samples (range 0.01-23 ng mg-1 protein). Using an arbitrary cut-off value of 0.15 ng mg-1 protein, 30% of the tumours were classified as manifesting p53 overexpression. Significant and independent correlations were found to exist between p53 overexpression and shorter disease-free (P < 0.001) and overall survival (P = 0.039) at a median duration of follow-up of 50 months. p53 overexpression was related to low oestrogen receptor content and high proliferation rate (S-phase fraction). No relationship was found to tumour size or the presence of lymph node metastasis. Three tumours possessed an extremely high p53 content (> 10 ng mg-1 protein), all of which were of medullary or high-grade ductal type, oestrogen and progesterone receptor negative, DNA non-diploid, had S-phase fractions of > 22% and recurred within 1-2 years. In summary, a new sensitive and quantitative LIA suitable for routine analysis of p53 protein in steroid receptor cytosol preparations from breast tumours has been developed to confirm the prognostic importance of p53 protein accumulation in human breast cancer.
  • Brismar-Wendel, S, et al. (författare)
  • Age-specific prevalence of HPV genotypes in cervical cytology samples with equivocal or low-grade lesions
  • 2009
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 101:3, s. 511-517
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To define the spectrum of human papillomavirus (HPV) types and establish an age limit for triage HPV testing in atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). MATERIALS AND METHODS: 343 liquid-based cytological samples from the population-based screening programme with minor abnormalities were subjected to HPV genotyping (Linear Array, Roche, Basel, Switzerland). RESULTS: High-risk human papillomavirus (HR-HPV) was found in 71% of LSIL and 49% of ASCUS cases (P<0.001). High-risk human papillomavirus prevalence was age-dependent in LSIL (P = 0.01), with decreasing prevalence until the age of 50 years, followed by a slight increase. Human papillomavirus type 16 was the most common HR-HPV, found in 23% of HPV-positive women. Human papillomavirus type 18 was the sixth most common, found in 9.9% (P<0.001). An age-dependent quadratic trend was observed for multiple infections (P=0.01) with a trough at about 42 years. The most common HR-HPV types to show a coinfection with HPV16 (clade 9) were HPV39 (28%), 45 (38%), and 59 (46%), belonging to HPV18 clade 7. The frequency of low-risk (LR) vs probable HR and HR-HPV also followed an age-dependent quadratic trend. CONCLUSIONS: After the age of 25 years, HR-HPV prevalence is similar in LSIL and ASCUS cases, motivating a low age limit for triage HPV testing. Multiple infections and LR/HR-HPV dominance are age-dependent. Genotyping in longitudinal design is needed to elucidate the importance of multiple infections in cancer progression and in cross-protection from vaccination. British Journal of Cancer (2009) 101, 511-517. doi:10.1038/sj.bjc.6605165 www.bjcancer.com Published online 21 July 2009 (C) 2009 Cancer Research UK
  • Brodin, Bertha A., et al. (författare)
  • Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas
  • 2019
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 120:4, s. 435-443
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. METHODS: We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations. RESULTS: Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient. CONCLUSIONS: Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.
  • Brooks, D. R., et al. (författare)
  • Temporal trends in non-small cell lung cancer survival in Sweden
  • 2007
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 96:3, s. 519-522
  • Tidskriftsartikel (refereegranskat)abstract
    • We modeled temporal trends in the 1- and 5-year survival of 32 499 patients with adenocarcinoma and squamous cell carcinoma of the lung in the Swedish Cancer Register between 1961 and 2000. The 1-year relative survival for adenocarcinoma improved from 37% for patients diagnosed 1961–1965 to 45% for those diagnosed 1996–2000 and from 39 to 45% for squamous cell carcinoma. The adjusted excess mortality ratios for the period 1996–2000 compared with 1961–1965 were 0.80 for adenocarcinoma and 0.81 for squamous cell carcinoma. Thus, a previous report in a Dutch study of a relatively worsening prognosis for adenocarcinoma over time could not be confirmed.
  • Carlsson, Jörgen, et al. (författare)
  • HER2 expression in breast cancer primary tumours and corresponding metastases : Original data and literature review
  • 2004
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 90:12, s. 2344-2348
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.
  • Cavalli-Björkman, Nina, 1970-, et al. (författare)
  • Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
  • 2012
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 107:1, s. 189-194
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 
  • Dyrskjot, L., et al. (författare)
  • Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
  • 2012
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 107:8, s. 1392-1398
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.
  • Eberhard, J., et al. (författare)
  • A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer
  • 2012
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 106:5, s. 931-938
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Special AT-rich sequence-binding protein 2 (SATB2) is a novel diagnostic marker of colorectal cancer (CRC), and loss of SATB2 has been linked to poor survival from the disease. In this study, we validated the prognostic ability of SATB2 expression in a large, prospective CRC cohort. METHODS: Immunohistochemical SATB2 expression was assessed in 527 incident CRC cases from the Malmo Diet and Cancer Study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB2 expression on cancer-specific survival (CSS) and overall survival (OS). RESULTS: High SATB2 expression was associated with a prolonged CSS in the full cohort (hazard ratio (HR)=0.61; 95% CI 0.41-0.92) and in colon cancer (HR=0.39; 95% CI 0.20-0.75), remaining significant in multivariable analysis of colon cancer (HR 0.49; 95% CI 0.25-0.96), with similar findings for OS. In curatively resected stage III-IV patients, a significant benefit from adjuvant and/or neoadjuvant therapy was observed for SATB2 high tumours (P-interaction 0.037 for OS) and high SATB2 expression in rectal cancer correlated with an enhanced effect of neoadjuvant therapy (P-interaction 0.033 for OS). CONCLUSION: High SATB2 expression is an independent marker of good prognosis in colon cancer and may modulate sensitivity to chemotherapy and radiation. British Journal of Cancer (2012) 106, 931-938. doi:10.1038/bjc.2012.34 www.bjcancer.com Published online 14 February 2012
  • Elander, N. O., et al. (författare)
  • Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer
  • 2018
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 118:7, s. 947-954
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy.METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA).RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009).CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.
  • Elander, N. O., et al. (författare)
  • Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy
  • 2018
  • Ingår i: British Journal of Cancer. - NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 118:8, s. 1084-1088
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma.METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups.RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group.CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.
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