Citations

Abstract The goal of this study was to assess the performance characteristics of the Automated Cellular Imaging System (ACIS III) for HER2 immunohistochemical analysis. The study was performed on 187 biopsy slides from patients who underwent HER2 testing between January and February 2008. Three scoring methods by the ACIS III were compared with the manual score and fluorescence in situ hybridization (FISH) results for HER2 amplification. The equal distribution score (EQD) method, in which 2 areas each of high-, moderate-, and low-intensity staining were measured, most closely matched the FISH HER2 amplification result. The numbers of immunohistochemically negative (0 or 1+)/FISH+ cases were equivalent for all methods. The EQD method had significantly fewer 2+ cases (n = 16) (P < .001) vs the manual method (n = 35) and yielded a higher positive predictive value (38%) for HER2 amplification compared with the manual method (20%). The EQD method may more accurately identify FISH-amplified HER2 cases with fewer 2+ cases that would be “reflexed” to FISH compared with the manual method.

Abstract Background: Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in >40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer. Methods: We investigated 60 polymorphisms in the TUBD1, SEPT4, PRKCA, TBX2, TBX4, TEX14, TLK2, YPEL2, and PPM1E genes from this amplicon for association with breast cancer risk among 798 Caucasian breast cancer cases and 843 unaffected Caucasian controls from the Mayo Clinic. Results: Eight polymorphisms in PRKCA, TBX4, TLK2, and YPEL2 displayed significant dose-response associations with breast cancer risk (Ptrend < 0.05). Of these, PRKCA rs7342847 and TLK2 rs2245092 and rs733025 were also associated with hormone receptor–positive breast cancer: PRKCA rs7342847 (odds ratio, 0.7; 95% confidence interval, 0.6-0.9; Ptrend = 0.002) and TLK2 rs733025 and rs2245092 (both: odds ratio, 0.8; 95% confidence interval, 0.7-1.0; Ptrend = 0.03). Interactions between SEPT4 rs758377 and TEX14 rs302864 (Pinteraction = 0.0003) and between TLK2 rs733025 and YPEL2 rs16943468 (Pinteraction = 0.05) for risk of breast cancer were also observed. Conclusion: These findings suggest that single polymorphisms and combinations of polymorphisms within candidate oncogenes from the 17q23 amplicon may influence risk of breast cancer overall and possibly specific molecular subtypes of breast tumors. The findings are discussed within the context of the results from two independent data sets. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1864–8)

Background and Purpose— Predictive models of outcome after ischemic stroke have incorporated acute diffusion-weighted MRI (DWI) information with mixed results. We hypothesized that serial measurements of DWI infarct volume would be predictive of functional outcome after ischemic stroke. Methods— The prospective Acute Stroke Accurate Prediction (ASAP) Study included a prespecified serial imaging subgroup who underwent DWI studies at baseline (<24 hours after symptom onset) and Day 5 (±2 days). DWI infarct volumes were calculated using the Analyze software (Rochester, Minn). Clinical outcomes were assessed at 3 months. Univariate and multivariable regression analysis was performed to assess the relationship between change in DWI lesion volume and excellent neurological outcome (modified Rankin Scale 0, 1, and Barthel Index ≥95). Results— In total, 169 cases from the ASAP study had serial DWI scans with a measurable lesion at baseline, follow-up, or both. The median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 3 to 13). For each 10 cm 3 of growth in DWI infarct volume, the OR for achieving an excellent outcome by modified Rankin Scale was 0.52 (95% CI, 0.38 to 0.71) and for the Barthel Index was 0.64 (95% CI, 0.51 to 0.79). Adjusting for clinically important covariates, the OR for an excellent modified Rankin Scale outcome was 0.57 (95% CI, 0.37 to 0.88) and excellent Barthel Index outcome was 0.75 (95% CI, 0.56 to 1.01). Conclusions— Based on these data, the likelihood of achieving an excellent neurological outcome diminishes substantially with growth in DWI infarct volume in the first 5 days after ischemic stroke of mild to moderate severity.

Background Different cerebrospinal fluid (CSF) amyloid-beta 1–42 (A β 1–42 ), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. Methods Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured A β 1–42 , Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. Results In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for A β 1–42 , Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest ® ( N = 13) for A β 1–42 , lower interCV were calculated (22%). The centres that participated in both years ( N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. Conclusions The highest variability was found for A β 1–42 . The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.

Introduction: To review the incidence and risks of bladder cancer following gastrointestinal augmentations done for congenial anomalies in childhood. Materials and Methods: A literature search using PubMed and Ovid Medline search engines was performed. MeSH terms evaluated were; bladder augmentations, enterocystoplasty, gastrocystoplasty, spina bifida, spinal dysraphism, myelodysplasia, neural tube defects, posterior urethral valves and bladder exstrophy were cross referenced with the terms, bladder cancer and urinary bladder neoplasm. All patients who developed a bladder cancer following a bladder augmentation for a congenital anomaly were reviewed Results: A total of 20 cases of bladder cancer following augmentations for congential anomalies, were identified, 9 arose following ileal cystoplasty, 3 following colocystolasty and 8 following gastrocystoplasty. The incidence of cancer developing per decade following surgery was 1.5% for ileal/colonic and 2.8% for gastric bladder augmentations. The majority of cancers developing within the augmented bladder are at advanced stages at the time of diagnosis (60%; 12/20 cases were ≥T3 at diagnosis). Several of the cases that developed occurred in patients exposed to known carcinogenic stimuli and/or arose in bladders with a known predisposition to carcinoma. Conclusion: Patients augmented with ileal or colonic segment for a congenital bladder anomaly have a 7—8 fold and gastric augments a 14—15 fold increased risk for the development of bladder cancer over standard norms. Published data is however unable to determine if gastrointestinal bladder augmentation is an independent risk factor for cancer over the inherent risk of cancer arising from a congenitally abnormal bladder.