Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening

Abstract

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

Strong Programmed Death Ligand 1 Expression Predicts Poor Response and De Novo Resistance to EGFR Tyrosine Kinase Inhibitors Among NSCLC Patients With EGFR Mutation

“…The PD-L1 prevalence in NSCLC detected via SP142 in PTEN-qualified samples is comparable to previous reports of Asian patients. 45 Therefore, our results should be further confirmed using a standardized method.…”

PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around

“…From a technical perspective, PTEN basal expression in stromal cells can be utilized as a control marker of tissue quality and, according to the acceptable expression levels, tissues can be analyzed with for PD-L1 or rejected. While exclusion of poor-quality samples is critical before biomarker analysis, the criteria for selecting PTEN as a tissue quality marker should be explored deeper [108]. IFN-γ-mediated anti-oncogenic functions are well demonstrated in cancer, including in lung cancer, and exogenous administration has been used to treat different malignancies and PTEN appears to play a role also in the IFN-γ impact.…”

Monitoring the Response of PD-L1 Expression to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Nonsmall-Cell Lung Cancer Xenografts by Immuno-PET Imaging

“…2 More than half of the NSCLC patients present with metastatic disease upon diagnosis and are no longer fit for surgery. 2 Platinum-based chemotherapy and radiotherapy are the standard-of-care options for these patients with NSCLC, yet only to provide limited improvements in survival. 3 Recently, vital breakthroughs in immunotherapies, especially the discovery of immune checkpoint blockade, have revolutionized cancer treatment, with the potential to elicit durable response and ultimately improve long-term survival.…”

“…Lung cancer is the leading cause of cancer mortality worldwide with an estimated 1.6 million deaths for the year 2017 . Nonsmall-cell lung cancer (NSCLC) is one of the two major types of lung cancer, comprising approximately 85% of all lung cancer cases . More than half of the NSCLC patients present with metastatic disease upon diagnosis and are no longer fit for surgery .…”