In this real world setting, high uptake of EGFR testing was achieved and associated with major changes in EGFR-TKI prescribing and improved health outcomes. Modifiable factors determined testing uptake. Study registration ACTRN12615000998549.

BackgroundThe use of Microarray (array CGH) analysis has become a widely accepted front-line test replacing G banded chromosome studies for patients with an unexplained phenotype. We detail our findings of over 5300 cases.ResultsOf 5369 pre and postnatal samples, copy number variants (CNVs) were detected in 28.3 %, of which ~40 % were deletions and ~60 % were duplications. 96.8 % of cases with a CNV <5 Mb would not have been detected by G banding. At least 4.9 % were determined to meet the minimum criteria for a known syndrome. Chromosome 17 provided the greatest proportion of pathogenic CNVs with 65 % classified as (likely) pathogenic. X chromosome CNVs were the most commonly detected accounting for 4.2 % of cases, 0.7 % of these being classified as cryptic (likely) pathogenic CNVs.ConclusionsMicroarray analysis as a primary testing strategy has led to a significant increase in the detection of CNVs (~29 % overall), with ~9 % carrying pathogenic CNVs and one syndromic case identified per 20 referred patients. We suggest these frequencies are consistent with other heterogeneous studies. Conversely, (likely) pathogenic X chromosome CNVs appear to be greater compared with previous studies.

BackgroundHydatidiform moles occur in approximately 1 in 1,500 pregnancies; however, early miscarriages or spontaneous abortions may not be correctly identified as molar pregnancies due to poor differentiation of chorionic villi.MethodsThe current clinical testing algorithm used for the detection of hydatidiform moles uses a combination of morphological analysis and p57 immunostaining followed by ploidy testing to establish a diagnosis of either a complete or partial molar pregnancy. We review here 198 referrals for fluorescence in situ hybridization (FISH) ploidy testing, where the initial diagnosis based on morphology is compared to the final diagnosis based on a combination of morphology, FISH and p57 immunohistochemical (IHC) staining.ResultsApproximately 40% of cases were determined to be genetically abnormal, but only 28.8% of cases were diagnosed as molar pregnancies. The underestimation of complete molar pregnancies and those with androgenetic inheritance was also found to be likely using conventional diagnostic methods, as atypical p57 staining was observed in approximately 10% of cases.ConclusionsOur findings suggest that a revised approach to testing products of conception is necessary, with cases screened according to their clinical history in order to distinguish molar pregnancy referrals from hydropic pregnancies.

To investigate the clinical validity and utility of tests for detecting Epidermal Growth Factor Receptor (EGFR) gene mutations in non-squamous non-small cell lung cancer patients, tumour DNA extracts from 532 patients previously tested by the cobas EGFR Mutation Test (RT-PCR test) were retested by the Sequenom/Agena Biosciences MassArray OncoFocus mass spectrometry test (MS test). Valid results from both tests were available from 470 patients (88%) for agreement analysis. Survival data were obtained for 513 patients (96%) and 77 patients (14%) were treated with EGFR tyrosine kinase inhibitors (TKIs). Agreement analysis revealed moderately high positive (79.8%), negative (96.9%) and overall percentage agreement (93.2%) for the detection of EGFR mutations. However, EGFR mutations were detected by one test and not by the other test in 32 patients (7%). Retesting of discordant samples revealed false-positive and false-negative results generated by both tests. Despite this, treatment and survival outcomes correlated with the results of the RT-PCR and MS tests. In conclusion, this study provides evidence of the clinical validity and utility of the RT-PCR and MS tests for detection of EGFR mutations that predict prognosis and benefit from EGFR-TKI treatment. However, their false-positive and false-negative test results may have important clinical consequences.

Background Lung cancer is a major cause of death in New Zealand. In recent years, targeted therapies have improved outcomes. Aim To determine the uptake of anaplastic lymphoma kinase (ALK) testing, and the prevalence, demographic profile and outcomes of ALK‐positive non‐small‐cell lung cancer (NSCLC), in New Zealand, where no national ALK‐testing guidelines or subsidised ALK tyrosine kinase inhibitor (TKI) therapies are available. Methods A population‐based observational study reviewed databases to identify patients presenting with non‐squamous NSCLC over 6.5 years in northern New Zealand. We report the proportion tested for ALK gene rearrangements and the results. NSCLC samples tested by fluorescence in situ hybridisation were retested by next generation sequencing and ALK immunohistochemistry. A survival analysis compared ALK‐positive patients treated or not treated with ALK TKI therapy. Results From a total of 3130 patients diagnosed with non‐squamous NSCLC, 407 (13%) were tested for ALK gene rearrangements, and patient selection was variable and inequitable. Among those tested, 34 (8.4%) had ALK‐positive NSCLC. ALK‐positive disease was more prevalent in younger versus older patients, non‐smokers versus smokers and in Māori, Pacific or Asian ethnic groups than in New Zealand Europeans. Fluorescence in situ hybridisation, ALK immunohistochemistry and next generation sequencing showed broad concordance for detecting ALK–positive disease under local testing conditions. Among patients with ALK‐positive metastatic NSCLC, those treated with ALK TKI survived markedly longer than those not treated with ALK TKI (median overall survival 5.12 vs 0.55 years). Conclusion Lung cancer outcomes in New Zealand may be improved by providing national guidelines and funding policy for ALK testing and access to subsidised ALK TKI therapy.

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Abstract. The aim of the present study was to evaluate the use of KaryoLite™ bacterial artificial chromosomes (BACs)-on-Beads™ (BoBs) technology for the rapid screening of products of conception (POC). Validation and prospective studies were carried out on 85 and 95 patient samples, respectively. Validation studies had previously been analyzed using routine culture and G-banded karyotyping. BoBs resulted in an abnormality detection frequency of 27%, with a failure rate of <3%. The time required for processing was significantly lower compared with that of tissue culture. In conclusion, BoBs technology decreased the failure rate, while increasing the analytical sensitivity compared with G-banded karyotype analysis alone. Additionally, significant cost savings may be achieved with regard to the time of processing and analysis of

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