Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies

<p>Abstract</p> <p>Background</p> <p>Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation.</p> <p>Aim</p> <p>To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies.</p> <p>Materials and methods</p> <p>315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs.</p> <p>Results</p> <p>Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree.</p> <p>Discussion</p> <p>Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.</p

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.Journal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tSCOPUS: re.jinfo:eu-repo/semantics/publishe

Dopamine Transporter SPECT Imaging in Corticobasal Syndrome

evidence of preserved nigral neuronal density. imaging evidence of preserved nigral terminals have been recently described.In this multicenter study, we investigated presynaptic nigrostriatal function in 36 outpatients fulfilling clinical criteria for “probable corticobasal degeneration” (age 71±7.3 years; disease duration 3.9±1.6 years), 37 PD and 24 healthy control subjects using FP-CIT single photon emission computed tomography. Clinical, neuropsychological, and magnetic resonance imaging assessment was performed to characterize CBS patients. Linear discriminant analysis was used to categorize normal vs. pathological scans.FP-CIT binding reduction in patients with CBS was characterized by larger variability, more uniform reduction throughout the striatum and greater hemispheric asymmetry compared to PD. Moreover, there was no significant correlation between tracer uptake values and clinical features such as disease duration and severity. Despite all CBS subjects showed obvious bilateral extrapyramidal signs, FP-CIT uptake was found to be normal bilaterally in four CBS patients and only unilaterally in other four cases. Extensive clinical, neuropsychological and imaging assessment did not reveal remarkable differences between CBS subjects with normal vs. pathological FP-CIT uptake.Our findings support the hypothesis that extrapyramidal motor symptoms in CBS are not invariably associated with SNc neuronal degeneration and that supranigral factors may play a major role in several cases. CBS individuals with normal FP-CIT uptake do not show any clinical or cognitive feature suggesting a different pathology than CBD

Scaling matters: incorporating body composition into Weddell seal seasonal oxygen store comparisons reveals maintenance of aerobic capacities

Adult Weddell seals (Leptonychotes weddellii) haul-out on the ice in October/November (austral spring) for the breeding season and reduce foraging activities for ~4 months until their molt in the austral fall (January/February). After these periods, animals are at their leanest and resume actively foraging for the austral winter. In mammals, decreased exercise and hypoxia exposure typically lead to decreased production of O2-carrying proteins and muscle wasting, while endurance training increases aerobic potential. To test whether similar effects were present in marine mammals, this study compared the physiology of 53 post-molt female Weddell seals in the austral fall to 47 pre-breeding females during the spring in McMurdo Sound, Antarctica. Once body mass and condition (lipid) were controlled for, there were no seasonal changes in total body oxygen (TBO2) stores. Within each season, hematocrit and hemoglobin values were negatively correlated with animal size, and larger animals had lower mass-specific TBO2 stores. But because larger seals had lower mass-specific metabolic rates, their calculated aerobic dive limit was similar to smaller seals. Indicators of muscular efficiency, myosin heavy chain composition, myoglobin concentrations, and aerobic enzyme activities (citrate synthase and β-hydroxyacyl CoA dehydrogenase) were likewise maintained across the year. The preservation of aerobic capacity is likely critical to foraging capabilities, so that following the molt Weddell seals can rapidly regain body mass at the start of winter foraging. In contrast, muscle lactate dehydrogenase activity, a marker of anaerobic metabolism, exhibited seasonal plasticity in this diving top predator and was lowest after the summer period of reduced activity