Immune checkpoint inhibitors have become important tools for managing NSCLC, can the analysis identify individuals with malignancies?
Reported in Journal of Molecular DiagnosticsThe analysis of small non-fixed tissue samples, assembled using minimally invasive bronchoscopy, immune control site inhibitors, can identify individuals with malignancy and give expression levels of PD-L1.
The tools to fight cancer
Immune control site inhibitors, such as the anti-PD-1 antibody pembrolizumab, have become important agents for the management of non-small cell lung cancer (NSCLC).
Determining the level of programmed death ligand 1 (PD-L1), expressed by a tumor, can help clinicians determine how the patient should be treated.
The report describes a new and fast approach to quantifying the expression levels of PD-L1 in tumors, which requires only small amounts of tissue that can be harvested using minimally invasive bronchoscopic techniques. This approach can also be used to distinguish malignant from benign tumors and identify mutational status, all of which can direct and improve therapeutic solutions.
Dr. Stephen Bozinovski from the School of Health and Biomedical Sciences, RMIT, Australia, explains: "The emergence of screening lung cancer studies will lead to greater demand for the molecular nature of suspected pulmonary nodules.
"This test has the potential to save considerable time and money to identify patients who are most likely to benefit from control point inhibitors such as pembrolizumab."
Is it possible for the immune control site inhibitors to be the new rationalized approach?
The paper describes a new rationalized approach for the complex molecular profile of bronchial specimens thought to be NSCLC. When collecting a bronchoscopic specimen by brush or EBON with a biopsy, a small amount of tissue is placed directly into the stabilizing nucleic acid buffer after a rapid on-site assessment of malignancy.
RNA and DNA were isolated from the sample and quantitative determination of the expression of matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor (TIMP3) was performed.
The test itself can be performed very quickly, so the diagnosis of malignancy and PD-L1 status can be determined within hours of collection. The test and evaluation can be easily automated to eliminate the variability of the test.
"In this study, we demonstrate for the first time that the MMP-9: TIMP3 ratio can accurately differentiate malignant from non-malignant tissue samples without the need to fix tissue for histological evaluation," adds Bozhinovski.
In one case, the MMP9: TIMP3 ratio was increased more than 300 times, whereas cytology was normal. Nine months later, repeat cytology confirms that the tumor is really malignant.
The assay selects patients with immune control site inhibitors
The assay also quantifies the levels of the PD-L1 transcript, which may have an important impact on the clinical management of NSCLC. Pembrolizumab has FDA approval for the front-line treatment of patients with advanced NSCLC whose tumors have 50% or more PD-L1 expression as determined by the SP263 immunohistochemical test. Patients with lower levels of PD-L1 expression are more likely to benefit from a combination of pembrolizumab and chemotherapy.
The study demonstrated a strong positive relationship between PD-L1 transcript levels measured by the new analysis and FDA-approved SP263 immunohistochemistry.
According to the researchers, enough genomic DNA from the same specimen should be available to allow several panels a purposefully next-generation sequence to evaluate the overall mutational burden of the tumor.
It is important that this is possible because the tissue is unfixed, maintaining the integrity of DNA and RNA. In this report, mutations were found in most of the EBUS tumor specimens, including TP53 gene mutations found in 10 of 15 NSCLC samples. Such information may further enhance the patient's selection for a particular treatment regimen.
The test offers additional benefits, including fast run time and automated analysis.
Bozhinovski concludes: "We believe our test should significantly improve the diagnostic utility of bronchoscopic EBUS samples for molecular examination of patients with lung cancer."