Guidance for laboratories performing molecular pathology for cancer patients

Abstract

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here.

The pathomorphologist’s role in the era of personalised therapy regarding the case of colorectal tumours

“…They can be divided into biomarkers whose expression is determined with immunohistochemistry methods and and/or the markers whose disorders in germinal or somatic cells are detected with molecular methods. They should undergo external quality control (EQC), which should be carried out among others by European organisations such as the European Society of Pathology (ESP) [6,7].…”

“…The moments of key significance for the quality of the correct results of the immunohistochemistry (IHC) and molecular tests are the pre-analytical stage (securing, preservation and technical processing of the tissue material), identification of the neoplastic tissue by the pathomorphologist for molecular tests and the validation and standardisation of the IHC and molecular methods. The work pattern in a modern pathology department according to the recommendations of the European and British pathological societies is illustrated in Figure 1 [6]. A pathomorphologist collaborating with an oncologist should have at their disposal a laboratory with automatic equipment which allow for obtaining repetitive results in the evaluation of biomarkers.…”

Techniques for maximizing the performance of molecular pathology testing: responsibilities of all pathologists

“…Macrodissection is sufficient in some large samples, and detailed microdissection may be necessary for specimens that may be considered particularly small and insufficient (3). If the tumor is heterogeneous, it may be necessary to mark multiple sites in multiple locations (4). As an alternative to macrodissection, a 1 mm punch can be taken from the marked areas or microdissection can be performed using a tissue counterstain under a stereoscopic microscope.…”

“…The interobserver reliability of the estimation of the percentage of tumor cells detected in pathological material varies widely among researchers. One of the main tasks that fall into histopathology evaluation today is to estimate tumor cell ratio, which is influential on the reliability and success of the molecular work to be performed (4). Comprehensive tumor cell counting may possibly yield more reliable numbers, but it is time-consuming.…”

El diagnóstico molecular en la praxis de la oncología en el Sector Salud. El laboratorio de oncología molecular como herramienta

“…4,5 Diferentes instituciones clínicas que atienden integralmente a los pacientes con cáncer bajo la modalidad de oncología personalizada se apoyan en las determinaciones de biomarcadores en laboratorios de oncología molecular (LOM), en donde actualmente se identifican más de cien biomarcadores moleculares en tejido tumoral que ayudan a precisar el diagnóstico, el pronóstico, la toma de decisiones terapéuticas, o son utilizadas en la valoración de la enfermedad mínima residual, y en células germinales para la determinación de marcadores oncogenéticos en casos de cáncer familiar. 5,6 Dentro de estos LOM, el del Hospital Universitario Central de Asturias, en España, que cumplió recientemente 10 años de su inicio, cuenta con condiciones asistenciales parecidas a las de los principales hospitales oncológicos del sector salud y podría ser un eventual modelo a emular.…”