Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Abstract

Background: There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC.

Methods: Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described.

Results: Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team.

Conclusions: To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential.

Keywords: Histology/Cytology; Non-Small Cell Lung Cancer.

Figure 1

Importance of manual microdissection as a prerequisite for reliable and reproducible analyses in molecular pathology. (A–D) A typical lung specimen with five biopsies, of which one contained malignant cells; only this biopsy should be used for molecular analyses. The tumour area must therefore be primarily prepared microscopically from the paraffin block before being analysed. (E) Further analytical steps. (F) Example of a pathology report combining morphological and molecular results as a prerequisite for treatment of a patient with a targeted drug. (G) All tests should be accompanied by external quality assurance, such as ‘Qualitätssicherungs-Initiative Pathologie’ (QuIP).

Figure 2

A realistic approach for sample prioritisation for the study of predictive biomarkers in patients with advanced lung adenocarcinomas. Route A is for cases that require classificatory immunohistochemistry (IHC), while route B is for cases that are diagnosed based on H&E staining alone. The relative frequency of the different genetic alterations is shown in parentheses. Adapted from Conde et al, under the Creative Commons Attribution licence (CC BY). AC, adenocarcinoma; ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homologue B1; EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor; KRAS, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue; NSCLC-NOS, non-small-cell lung cancer-not otherwise specified; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.