The Relevance of External Quality Assessment for Molecular Testing for ALK Positive Non-Small Cell Lung Cancer:Results from Two Pilot Rounds Show Room for Optimization

Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012-2013.Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images.Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images.There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing

Simultaneous detection of lung fusions using a multiplex RT-PCR next generation sequencing-based approach:A multi-institutional research study

Contains fulltext : 195300.pdf (publisher's version ) (Open Access

Endorsing good quality assurance practices in molecular pathology: risks and recommendations for diagnostic laboratories and external quality assessment providers

Quality assurance is an indispensable element in a molecular diagnostic laboratory. The ultimate goal is to warrant patient safety. Several risks that can compromise high quality procedures are at stake, from sample collection to the test performed by the laboratory, the reporting of test results to clinicians, and the organization of effective external quality assessment schemes. Quality assurance should therefore be safeguarded at each level and should imply a holistic multidisciplinary approach. This review aims to provide an overview of good quality assurance practices and discusses certain risks and recommendations to promote and improve quality assurance for both diagnostic laboratories and for external quality assessment providers. The number of molecular targets is continuously rising, and new technologies are evolving. As this poses challenges for clinical implementation and increases the demand for external quality assessment, the formation of an international association for improving quality assurance in molecular pathology is called for.status: publishe

DESA1002 'Continuous City' Mary Lum

With a canal penetrating the Plaza Mayor on one side and a narrow, busy street on the other, my building sits amidst the bustling lifestyle of Madrid, Spain. Initially I had planned to design a cinema complex; however this idea developed and I eventually found myself devising plans for an auction house. The form of this building follows the function as well as the perimeter of the chosen area. Responding to the need for two separate paths of circulation in order to isolate public and private spaces, the lower levels of this building is essentially divided into two halves. One half is an auction theatre where auctions are held whilst the other half is dedicated to exhibition space. This is emphasised in the cladding of the building as one half is clad in opaque material whilst the other half is enclosed using transparent trace paper. Since the auction theatre is an enclosed space where lighting and temperature needs to be controlled with precision in order to create an appropriate environment for auctions, natural sun penetration is not needed. Therefore this half has been clad with the opaque material. On the other hand, I have designed the transparent exhibition area to have double ceiling height with the idea of glorifying artifacts and other auction items in mind. This is analogous to the notion that in high class restaurants, minute amounts of expensive food are served on large plates; framing it and accentuating its value. The top two levels of this building are dedicated to office space and grandiose meeting areas for important clients and business. These areas are located on the top floor as its transparency allows for the best views. The underground level on the other hand is used for storage and circulation space. The large vacant circulation area allows for large trucks to enter the building for deliveries

External Quality Assessment Unravels Interlaboratory Differences in Quality of RAS Testing for Anti-EGFR Therapy in Colorectal Cancer

Regulations for the selection of patients with metastatic colorectal cancer for anti-EGFR treatment changed at the end of 2013. The set of mutations to be tested extended from KRAS codons 12 and 13 to KRAS and NRAS exons 2, 3, and 4. A European external quality assessment scheme monitored the performance of laboratories and evaluated the implementation of the new regulations.status: publishe

Higher Quality of Molecular Testing, an Unfulfilled Priority: Results from External Quality Assessment for KRAS Mutation Testing in Colorectal Cancer

Precision medicine is now a key element in clinical oncology. RAS mutational status is a crucial predictor of responsiveness to anti-epidermal growth factor receptor agents in metastatic colorectal cancer. In an effort to guarantee high-quality testing services in molecular pathology, the European Society of Pathology has been organizing an annual KRAS (alias Ki-ras) external quality assessment scheme since 2009. In 2012, 10 formalin-fixed, paraffin-embedded samples, 8 from invasive metastatic colorectal cancer tissue and 2 artificial samples of cell line material, were sent to more than 100 laboratories from 26 countries with a request for routine KRAS testing. Both genotyping and results were assessed independently. Twenty-seven percent of the participants genotyped at least 1 of 10 samples incorrectly. In total, less than 5% of the distributed specimens were genotyped incorrectly. Genotyping errors consisted of false negatives, false positives, and incorrectly genotyped mutations. Twenty percent of the laboratories reported a technical error for one or more samples. A review of the written reports showed that several essential elements were missing, most notably a clinical interpretation of the test result, the method sensitivity, and the use of a reference sequence. External quality assessment serves as a valuable educational tool in assessing and improving molecular testing quality and is an important asset for monitoring quality assurance of incorporation of new biomarkers in diagnostic services.status: publishe

RAS testing practices and RAS mutation prevalence among patients with metastatic colorectal cancer: results from a Europe-wide survey of pathology centres

BACKGROUND: Treatment options for patients with metastatic colorectal cancer (mCRC) include anti-epithelial growth factor therapies, which, in Europe, are indicated in patients with RAS wild-type tumours only and require prior mutation testing of "hot-spot" codons in exons 2, 3 and 4 of KRAS and NRAS. The aim of this study was to evaluate the implementation of RAS testing methods and estimate the RAS mutation prevalence in mCRC patients. METHODS: Overall, 194 pathology laboratories were invited to complete an online survey. Participating laboratories were asked to provide information on their testing practices and aggregated RAS mutation data from 20 to 30 recently tested patients with mCRC. RESULTS: A total of 96 (49.5 %) laboratories across 24 European countries completed the survey. All participants tested KRAS exon 2, codons 12 and 13. Seventy (72.9 %) laboratories reported complete testing of all RAS hot-spot codons, and three (3.1 %) reported only testing KRAS exon 2. Sixty-nine (71.9 %) laboratories reported testing >80 patients yearly for RAS mutation status. Testing was typically performed within the reporting institution (93.8 %, n = 90), at the request of a treating oncologist (89.5 %, n = 85); testing methodology varied by laboratory and by individual codon tested. For laboratory RAS testing, turnaround times were </=10 working days for the majority of institutions (90.6 %, n = 87). The overall crude RAS mutation prevalence was 48.5 % (95 % confidence interval: 46.4-50.6) for laboratories testing all RAS hot-spot codons. Prevalence estimates varied significantly by primary tumour location, approximate number of patients tested yearly and indication given for RAS testing. CONCLUSION: Our findings indicate a rapid uptake of RAS testing in the majority of European pathology laboratories

External Quality Assessment Unravels Interlaboratory Differences in Quality of RAS Testing for Anti-EGFR Therapy in Colorectal Cancer

Contains fulltext : 155246.pdf (publisher's version ) (Closed access)BACKGROUND: Regulations for the selection of patients with metastatic colorectal cancer for anti-EGFR treatment changed at the end of 2013. The set of mutations to be tested extended from KRAS codons 12 and 13 to KRAS and NRAS exons 2, 3, and 4. A European external quality assessment scheme monitored the performance of laboratories and evaluated the implementation of the new regulations. MATERIALS AND METHODS: The 131 participating laboratories received 10 samples of formalin-fixed paraffin-embedded material, including RAS (exon 2, 3, 4) and BRAF mutations. Mock clinical data were provided for three cases. Using their routine methods, laboratories determined the genotypes and submitted three written reports. Assessors scored the results according to predefined evaluation criteria. RESULTS: Half of the participants (49.3%) had completely implemented the new test requirements (codons 12, 13, 59, 61, 117, and 146 of KRAS and NRAS), and 96 laboratories (73.3%) made no genotype mistakes. Correct nomenclature, according to the Human Genome Variation Society, was used by 82 laboratories (62.6%). CONCLUSION: Although regulations were effective for several months, many laboratories were not ready for full RAS testing in the context of anti-EGFR therapy. Nevertheless, in each participating country, there are laboratories that provide complete and correct testing. External quality assessments can be used to monitor implementation of new test regulations and to stimulate the laboratories to improve their testing procedures. Because the results of this program are available on the website of the European Society of Pathology, patients and clinicians can refer test samples to a reliable laboratory