Metastatic non-small cell lung cancer (NSCLC) therapy, in the last two decades, by focusing on the molecular profile of tumor cells to a large extent driven by histology and treatment strategies has changed. A mutation in lung cancer cells, amplification, insertion, deletion and includes many chromosomal abnormalities such as translocation.
That promotes tumor growth, gene amplification, point mutations, or re-transmission of signal pathways, resulting in oncogenic fusion proteins lead to the uncontrolled structural modification. Aberrant activation of the cell survival signal the continuation of when it is connected to oncogene addiction is emerging. The mutations that lead to oncogene addiction driver (driver) mutations is. Driver mutations/genetic changes are very sensitive to treatments that target tumors with gene products.
Who, when, how?
Nowadays, EGFR mutations, ALK and ROS1 rearanjman and PD-L1 testing is the most important molecular studies.
- All of advanced stage and metastatic disease presenting with non– squamous non-small cell lung carcinoma (NSCLC) in patients with concurrent at the time of finalization of the diagnostic –EGFR mutation ALK and ROS1 rearranjman tests should be requested. Each simultaneous testing of biomarkers, molecular and ensures the preservation of tissue samples increases the effectiveness of testing. The clinician's (if appropriate tumor tissue of adenocarcinoma of the components must not be excluded because of less, smoked – a long time ago left) should be performed in patients with squamous cell carcinoma patient.
- Molecular testing has not been performed previously developed in a progression or recurrence in patients with early-stage molecular EGFR, ALK and ROS1 should be made of EST (New biopsy is preferred).
- Molecular testing in patients with early stage disease at diagnosis is supported, but the final decision on this issue should be taken as specific to each Center a multidisciplinary oncology team.
- Previously, we conducted a molecular test patients with local progression and metastasis of tumors in the case of the development of Molecular Evolution (histological transformation, new mutations), due to the progression and treatment resistance in each phase of testing to be performed, it is recommended that new examples of molecular.
- After initial TKI response if there is metastasis, nodes can be tested.
- For patients with multiple primary lung adenocarcinomas and are independent of each other obviously, each test can be applied for tumor, but a single field for multiple different tumor testing is not required.
Reflex test : Ideally, it should be tested in patients in whom the pathology is determined at the time of diagnosis is able to do tests without prompt. Therefore, if possible, the characteristics of the patient and the stage of the request, it is recommended that requests be specified. This approach provides a result in a shorter period of the test. Ensuring that patients receive the right treatment at the right time plays an important role in personalized.
Bespoke test : When there is the need of molecular tests will be done on request. Since these tests can be done at a later time must be stored tissue. These tests will not be a waste of time and money that will be performed when necessary. However, the request has been made after the conclusion takes a long time.
Total reporting period end:
Reporting time for all tests 10 business days (2 weeks) as recommended.
The Importance Of Multidisciplinary Approaches In Lung Cancer
With good communication between the clinician and the pathologist:
- The doctor who performs the operation, the molecular study for acquired resistance in doubt, especially when the biopsy taken from the lesion growing, it is important to know
- The first of the molecular study need to be made when the pathologist to inform
- Formalin exposure limit their time day or the previous day of a vacation day Friday's of samples to take,ensuring not to
- Notification of the need of special treatment as a priority for the protection of material be made,
- The purpose of the process in which molecular or specific help is provided for tests that there are to be known.
Lung adenocarcinoma tumors and adenocarcinoma components that the exclusion of EGFR mutations, ALK and ROS-1 it is recommended that it be consulted.
Mandatory testing tests targeted to the genes in the category
Simultaneously EGFR mutation ALK and ROS-1 molecular tests for rearranjman
Genes in the latter category (B-raf, MET, Erb-B2 [HER2], Ret, K-ras)
Types Of The Tumor To Be Tested
Small cell carcinoma:
- Adenocarcinoma
- Adenosquamous carcinoma
- Large cell carcinoma
- NSCLC-NOS
Tumor Types That Are Not Offered Testing
- Neuroendocrine carcinoma Pur
- Pur-small cell carcinoma
- Pur squamous cell carcinoma
• In case of high clinical suspicion:
- Genç <50 yaş, hiç sigara içmemiş veya az içmiş hastalarda EGFR, ALK and ROS1 histology adenocarcinoma tumors on the outside of the test can be applied.
Molecular tests to be applied in sections to be used for selection of lung cancer
A pathologist should be included in the selection of molecular tests to be used for sections, and in the selection process, the structure of the tumor, Cytology and on the sample quality should be evaluated.
Pathologists, molecular biomarkers of lung cancer samples of the existing tests in order to determine whether they contain cancer cells is sufficient for these examples, the amount of tissue the level of protection and should evaluate the quality and quantity of nucleic acid.
Should be evaluated in terms of the content of each tumor sample and, when necessary, for the enrichment of tumor cells mikrodiseksiyon/makrodiseksiyon should be made in the process.
Molecular testing of samples that contain minimal tumor cells during the reporting-related restrictions and warnings must be specified. Although it is always valuable-positive results, negative results, if interpreted carefully, it should be kept in mind that the test result may be invalid.
To test the amount of tumor/tumor and the number of cells used method for each laboratory should be confirmed. At least 20ng DNA sequencing (300-400 cells), the fish test is required for live cell 50-100.
Molecular tests for the patient or to prevent a waste of time sufficient for tumor cells, this information should be shared immediately with oncology and pulmonologist
EGFR mutation need to be included in the test report
- Patient information
- The properties of the material tested (IIA paraffin blocks, etc.)
- Tissue (lymph nodes, lungs, brain, etc.)
- Pathological diagnosis
- Percentage of tumor
- Methods
- The analytical sensitivity of the test
- The tested exons
- Mutation status
- Comment on the results
ALK and ROS-1 rearranjman need to be included in the Report Analysis Report
- Patient information
- The properties of the material tested (IIA paraffin blocks, etc.)
- Tissue (lymph nodes, lungs, brain, etc.)
- Pathological diagnosis
- Number of cells and the percentage of tumor
- The method that is used:
- Immunohistochemistry: Antibody (clone) and platform used
- FISH: methods and probes
- The threshold value
- Conclusion: the analysis was performed in the nucleus of the number, and mutation status
- Comment on the results
Are being sent to another lab for molecular testing.
In cases where it is shipped to another laboratory for molecular testing of tumor cells may be because of the particular difficulties of containing a small amount of examples. A certain number of the cross-section sufficient for all the work that is requested to be sent to the lack of material in the wrong section or slice thickness necessary for the test, such as the lack of positive charged on the lam may cause difficulties.
Laboratories, paraffin blocks with pre-cut slides by sending depleted tissues in the case of other available materials based on molecular tests to be completed at the time may allow.
Diagnostic and PD-L1 (programmed death – ligand 1) with immunohistochemical study ALK and ROS1 test (IHC/fish) for at least 4-6; 4-µm sections, EGFR 10 µm cross section 2-3 pieces for mutation testing is required.
Previously painted sections and immunohistochemical tests to be done to be sent to the lab will help a lot. In cases where the tap is not enough, painted tissue scraped or fade out on the sections can be tested by molecular study for tests.
