Scientific background

Panel of authors:
Prof. Aleš Ryška, M.D., Ph.D. (Fingerland’s Department of Pathology, University Hospital Hradec Kralove)
Prof. Luboš Petruželka, M.D., Ph.D. (Department of Oncology, General University Hospital in Prague)
Prof. Jana Skřičková, M.D, Ph.D. (Department of Pulmonary Diseases and Tuberculosis, University Hospital Brno)
Prof. Vítězslav Kolek, M.D., Ph.D. (Department of Pulmonary Diseases and Tuberculosis, University Hospital Olomouc)
Assoc. Prof. Marián Hajdúch, M.D., Ph.D. (Institute of Molecular and Translational Medicine, University Hospital Olomouc)
Radoslav Matěj, M.D., Ph.D. (Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague)
Magdalena Uvírová, M.Sc. (CGB Laboratory JSC, Ostrava)
Prof. Miloš Pešek, M.D., Ph.D. (Department of Pulmonary Diseases and Tuberculosis, University Hospital Plzen)
Jana Dvořáčková, M.D., Ph.D. (University Hospital Ostrava)
Helena Hornychová, M.D., Ph.D. (Fingerland’s Department of Pathology, University Hospital Hradec Kralove)

1. Who should undergo genetic tests and when?

All NSCLC patients should undergo genetic testing for the presence of EGFR mutation at the moment of establishing the morphological diagnosis (adenocarcinoma, NSCLC - probably adenocarcinoma, NSCLC NOS). Evaluation for ALK rearrangements should be performed in all patients in which: (1) treatment with crizotinib is considered, (2) morphological diagnosis of adenocarcinoma, NSCLC probably adenocarcinoma or NSCLC NOS has been established, and (3) EGFR mutation has not been proved. Patients should not be selected depending on clinical factors (sex, smoking status, age, ethnicity). Genetic testing should be performed automatically. Technical and logistic details of testing will be defined by individual centres. The definitive morphological diagnosis will be established by a pathologist based on tumour histology or cytology according to the current ERS/ATR guidelines. In case of a tumour relapse, a new sample should be taken and tested.

2. How should genetic tests be performed?

Each centre performing molecular-genetic testing should develop its own procedure, and agree on a mutual cooperation with pathologists and clinicians. In general, if the amount of sampled material is not sufficient, it is necessary to either take a new sample, or to give up testing in that patient. Genetic changes can be detected in both histological and cytological samples. A morphological conformation of parallel histological samples in a single workplace is essential (samples must not be divided and sent to two distinct pathological centres); molecular genetics can be performed solely on samples which provably contain tumour elements. In general, any material suitable for a morphological diagnosis is also suitable for a molecular-genetic evaluation.

A close cooperation between a histopathological laboratory and a molecular genetic laboratory is essential, supplemented with an external quality control, or at least a comparison of samples between the laboratories. If possible, a CE-IVD certified kit can be used for the diagnosis. A centre performing tests for EGFR mutations must be capable of performing molecular genetic evaluations by at least two independent methods.

3. Interdisciplinary cooperation: how should it work?

The cooperation between pathologists and pulmonary oncologists plays a crucial role in ensuring a smooth run of the entire laboratory diagnostic process. An interdisciplinary cooperation must be established on the regional level. It is necessary to take into account that the evaluation is time-consuming; nevertheless, the entire process should not exceed 3 weeks after sampling the material. A smooth and quick transport must be ensured in order to minimise the delay.

Published [in Czech language only] in Studia pneumologica et phthiseologica 2012; 72(3): 168