Jansson S.,Lund University |
Bendahl P.-O.,Lund University |
Grabau D.A.,Lund University |
Falck A.-K.,Hospital of Helsingborg |
And 3 more authors.
Background: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer with poor prognosis and no targeted therapy available. Receptor tyrosine kinases (RTKs) are emerging targets in anticancer therapy and many RTKinhibiting drugs are currently being developed. The aim of this study was to elucidate if there is a correlation between the protein expression of three RTKs c-KIT, VEGFR2 and PDGFRa, their gene copy number, and prognosis in TNBC compared to non-TNBC. Methods: Tumor tissue samples from patients diagnosed with primary breast cancer were stained with immunohistochemistry (IHC) for protein assessment, and with fluorescence in situ hybridization (FISH) for gene copy number determination. Breast cancer mortality (BCM), measured from the date of surgery to death, was used as endpoint. Results: The cohort included 464 patients, out of which 34 (7.3%) had a TNBC. High expression of the three RTKs was more common in TNBC compared to non-TNBC: c-KIT 49% vs. 10% (P<0.001), PDGFRα 32% vs. 19% (P = 0.07) and VEGFR2 32% vs. 6% (P<0.001). The odds ratio (OR) of c-KIT, VEGFR2 and PDGFRα positivity, adjusted for tumor characteristics, was 6.8, 3.6 and 1.3 times higher for TNBC than for non-TNBC. 73.5% of the TNBC had high expression of at least one of the three investigated receptors, compared to 30.0% of the non-TNBC (P,0.001). Survival analysis showed no significant difference in BCM for TNBC patients with high vs. low c-KIT, PDGFRα or VEGFR2 protein expression. 193 (42%) tumors were evaluated with FISH. No correlation was seen between increased gene copy number and TNBC, or between increased gene copy number and high protein expression of the RTK. Conclusion: c-KIT, VEGFR2 and PDGFRa show higher protein expression in TNBC compared to non-TNBC. Further investigation clarifying the importance of these RTKs in TNBC is encouraged, as they are possible targets for anticancer therapy. © 2014 Jansson et al. Source
Ignell C.,Hospital of Helsingborg |
Berntorp K.,Skane University Hospital
Scandinavian Journal of Clinical and Laboratory Investigation
In 55 women with previous gestational diabetes mellitus, simultaneous capillary and venous plasma glucose concentrations were measured at 0, 30 and 120 min during a 75 g oral glucose tolerance test (OGTT). The aims of the study were to examine the relationship between capillary and venous glucose measurements, and to establish equations for the conversion of capillary and venous glucose concentrations using the HemoCue Glucose 201+ system. Additionally, the correlation between the capillary and venous glucose concentrations with the diagnostic cut-off limits proposed by the World Health Organization (WHO) in 1999 was evaluated. Capillary glucose concentrations were consistently higher than venous glucose concentrations at all time points of the OGTT (p < 0.001), and the correlations between the measurements were statistically highly significant (p < 0.001). The differences between the samples were greatest in the non-fasting state as revealed by the 95% prediction intervals (mmol/L) in Bland-Altman plots; ± 0.54 at 0 min, ± 2.01 at 30 min, and ± 1.35 at 120 min. Equivalence values for capillary plasma glucose concentrations derived from this study tended to be higher than those proposed by the WHO as diagnostic cut-off limits. Stratifying subjects by glucose tolerance status according to the WHO criteria revealed disagreements related to glucose values close to the diagnostic cut-off points. The study findings highlight the uncertainty associated with derived equivalence values. However, capillary plasma glucose measurements could be suitable for diagnostic purposes in epidemiological studies and when translating results on a group basis. © 2011 Informa Healthcare. Source
Kjolvmark C.,Hospital of Helsingborg |
Kjolvmark C.,Skane University Hospital |
Tschernij E.,Skane University Hospital |
Oberg J.,Skane University Hospital |
And 3 more authors.
Diagnostic Microbiology and Infectious Disease
Asymptomatic bacteriuria (ABU) is highly prevalent among elderly patients. It can be difficult to distinguish ABU from symptomatic urinary tract infection (UTI) in this population, which leads to unnecessary antibiotic treatment. Urinary heparin-binding protein (U-HBP) and urinary interleukin-6 (U-IL-6) have previously been studied as diagnostic markers for UTI. In this study, biomarkers were measured in the urine of 134 nursing home residents. The prevalence of ABU in this population, excluding patients with urinary catheter, was 32.8%. Levels of U-HBP and IL-6 were significantly lower among residents with ABU when compared to 49 patients with verified UTI. When previously defined cut-off limits were used, U-HBP had a high negative predictive value for UTI (93%), however, the specificity for differentiating patients with UTI and ABU was low. Discriminatory values were better for U-IL-6 with a sensitivity of 80% and specificity of 82% for the differentiation between the subgroup of pyelonephritis and ABU. © 2016 Elsevier Inc. Source
Falck A.-K.,Lund University |
Bendahl P.-O.,Lund University |
Ingvar C.,Lund University |
Ingvar C.,Skane University Hospital |
And 9 more authors.
Background: Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer.Methods: Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately.Results: DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63-2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples.Conclusions: The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow. © 2012 Falck et al.; licensee BioMed Central Ltd. Source
Olsen H.,Hospital of Helsingborg |
Nordenstrom E.,Skane University Hospital |
Bergenfelz A.,Skane University Hospital |
Nyman U.,Hospital of Trelleborg |
And 2 more authors.
Evaluation of subclinical hypercortisolism (SH) in patients with adrenal incidentaloma (AI) including its correlation to size, attenuation at unenhanced computed tomography (CT) and unilateral or bilateral adrenal disease. Nine hospitals in Southern Sweden investigated during 2005-2007 consecutively patients with AI with hormonal and CT examinations according a regional protocol. Two hundred and twenty-eight patients with AI with median size 2.0 cm were included. One mg overnight dexamethasone suppression test (DST) was performed in 223 patients and basal P-ACTH measured in 146 patients. SH was defined as cortisol ≥50 nmol/l at DST in combination with basal ACTH <2 pmol/l. In patients with unilateral AI 42% (76/180) had inadequate suppression at DST and 23% (27/115) had SH. The probability for SH and inadequate suppression at DST correlated positively to size and inversely to attenuation at CT. Bilateral AI were found in 43 patients and of these 70% (30/43) had inadequate suppression at DST and 42% (13/31) SH. The patients with SH or inadequate suppression at DST had increased frequency of hypertension which increased further in patients with post-DST cortisol ≥140 nmol/l. The applied criterion for SH is useful for initial evaluation of patients with AI. SH is common in patients with AI, particular in bilateral disease. In patients with unilateral AI the probability for SH correlated positively to size and inversely to attenuation at CT. Furthermore, SH and the post-DST cortisol concentration was associated with hypertension. © Springer Science+Business Media, LLC 2012. Source