You want to give the best treatment to your client/patient diagnosed with lung cancer but you are at sea concerning how to go about it. Read on to find out more.
Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively.
Indications for molecular testing.
The important reason for molecular testing of lung cancers is to select patients who may benefit from targeted therapies. In addition, patients with lung cancer can get benefits from molecular testing of their tumors regardless of stage. For example, molecular testing can provide accurate information on staging (in case of multiple tumors), prognostic stratification, and prompt treatment in case of recurrence. Because of the high frequency of EGFR mutations in Asian populations as mentioned above, EGFR mutation testing is especially important for the treatment of Korean lung cancer patients. Other mutations can also be approved and used as predictive markers in the near future. Each mutation is significantly associated with some clinical factors or histological subtypes.
Nevertheless, clinical findings alone cannot completely predict specific mutation status. In most of the guidelines published so far, histological types have been recommended as the most important factor in determining whether to perform molecular tests. In particular, for patients who have a diagnosis of non- small cell lung carcinoma (NSCLC) with an adenocarcinoma component or non-squamous cell type, molecular testing is routinely recommended. Thus, pathologists should try to further classify NSCLCs into more specific subtypes, such as adenocarcinoma or squamous cell carcinoma (SQC). Besides histological analysis, in cases of young age, female gender, never-smokers, small biopsies, or patients with a combined tumor type, molecular testing can be done.
Procedure
Formalin-fixed, paraffin-embedded (FFPE) tissues are most frequently used in molecular testing. Routinely prepared FFPE tissues are the most practical resource for molecular analysis, in spite of fixation-related artifacts. The optimal fixative for preparing FFPE samples is generally 10% neutral-buffered formalin. The optimal fixation time ranges from 6 to 72 hours to avoid underfixation or overfixation, respectively. Routinely prepared cytology samples such as alcohol-fixed smears or Thin Prep slides and cell block samples are also suitable for mutation testing.
Sample requirements
The presence of tumor cells in a sample must be confirmed before mutation analysis. The percentage and quality of tumor cells are crucial for proper mutation testing. For example, direct sequencing requires at least 20% tumor cells in the sample for reliable testing result.
Methodology
At TSL, lung biopsy samples are processed and histology reports are given within 5 working days following which molecular testing is done if requested for. EGFR testing is done by PCR, ALK by immunohistochemistry and FISH while PD-L1 is done by immunohistochemistry. Molecular testing reports are usually available within two weeks.