Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe

Abstract

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe.

Keywords: Molecular pathology; Next generation sequencing; Proficiency testing; Quality assessment; Quality assurance; Tumor testing.

Figure 1

Proposed model for the interaction between the EQA providers, the National Body and ISO 15189‐accredited laboratories. Each European country has an independent National body with a mandate to enforce laboratories to become ISO 15189 accredited and to participate in EQA schemes. In case of poor performance, there will be an encouraging interaction between the EQA provider and the laboratory. In case of persistent poor performance, the EQA provider will communicate this to the National Body who will undertake adequate steps.

Figure 2

Proposed framework for the organization of EQA schemes in Europe. EQA programmes are organized under supervision of the European Society for Pathology and/or a European Quality Assurance Council (van Krieken et al., 2008). A European organization for the coordination of EQA schemes determines in collaboration with representatives from the different participating countries and the EQA providers which schemes should be provided. One or several EQA provider(s) coordinate(s) collecting representative tissues or in silico data and distribution of a scheme as well as evaluation and feedback of the performance to all participating laboratories and in case of persistent poor performance to a National Body as depicted in Figure 1.