Correlation between Programmed Death Ligand-1(PD-L1) Expression and Driver Gene Mutations in Non-Small Cell Lung
Rahul Kumar Pandey1,2, Saumya Shukla1, Nuzhat Husain1
1Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, (UP), India.
Background:
Targeted therapy in adenocarcinoma is recommended. The use of immune check point inhibitors for the treatment of Non-small cell lung carcinoma (NSCLC) is used as both first-line and the second-line treatment strategy. The current study was undertaken to assess the frequency of programmed cell death ligand-1 (PD-L1) expression with anaplastic lymphoma kinase (ALK), proto-oncogene 1, receptor tyrosine kinase (ROS), epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), and v-Raf murine sarcoma viral oncogene homolog B (BRAF)V600E driver gene mutations in NSCLC adenocarcinoma phenotype. It assesses the frequencies of all markers in the cases where both treatment strategies can be implemented. Expression of the all markers was further compared with demographic, clinical parameters, and overall survival rate.
Materials And Methods:
The formalin-fixed paraffin-embedded (FFPE) tissue blocks were used in immunohistochemistry (IHC) staining and real-time polymerase chain reaction (RT-PCR) for determining the driver genes and PD-L1 expression in the 100 NSCLC-Adenocarcinoma cases.
Results:
PD-L1 positivity was observed in 26.36% (n=29/110) cases in adenocarcinoma. No significant differences in PD-L1 expression were observed among patients harboring ALK, ROS1, EGFR, KRAS, and BRAF mutations EGFR mutations had significant association with smoking status. (p= 0.008), Thyroid transcription factor 1 (TTF1) (p=0.0005) and Napsin (p=0.002) expression. ALK gene re-arrangement was significantly related to age (p= 0.001), gender (p= 0.009) and smoking status (p= 0.043). The single versus multiple driver mutations were significantly correlated with smoking status (p=0.005). In the survival rate analysis, EGFR (p=0.058), KRAS (p=0.021), and PD-L1 (p=0.039) were significantly high with the positive versus negative group.
Conclusions:
The current study is a novel attempt to document the co-expression of multiple driver mutations in the NSCLC-adenocarcinoma phenotype. PD-L1 immunopositivity in NSCLC-adenocarcinoma was higher with EGFR mutation as compared to those of KRAS, ALK, ROS, and BRAF driver genes.
Insights
This study found that programmed cell death ligand-1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) adenocarcinoma was higher with epidermal growth factor receptor (EGFR) mutations. PD-L1 positivity was also linked to improved survival rates in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapy and immune checkpoint inhibitors are key treatments for Non-small cell lung carcinoma (NSCLC) adenocarcinoma.
- Assessing programmed cell death ligand-1 (PD-L1) expression alongside driver gene mutations (ALK, ROS1, EGFR, KRAS, BRAF) is crucial for treatment strategies.
- Understanding the co-expression patterns of these markers can inform personalized treatment approaches.
Purpose of the Study:
- To determine the frequency of PD-L1 expression in NSCLC adenocarcinoma.
- To investigate the co-occurrence of PD-L1 expression with common driver gene mutations (ALK, ROS1, EGFR, KRAS, BRAF).
- To analyze the correlation between these markers, clinical parameters, and patient survival.
Main Methods:
- Immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) were used on 100 NSCLC-adenocarcinoma tissue samples.
- PD-L1 expression levels were quantified.
- Driver gene mutations and rearrangements were identified.
Main Results:
- PD-L1 positivity was found in 26.36% of cases.
- No significant difference in PD-L1 expression was observed across different driver mutations (ALK, ROS1, EGFR, KRAS, BRAF).
- EGFR mutations were associated with smoking status, TTF1, and Napsin expression. ALK rearrangements correlated with age, gender, and smoking status. EGFR, KRAS, and PD-L1 positivity were linked to higher survival rates.
Conclusions:
- This study highlights the co-expression of multiple driver mutations in NSCLC adenocarcinoma.
- PD-L1 immunopositivity was more frequent in NSCLC-adenocarcinoma with EGFR mutations compared to other driver genes.
- PD-L1 expression and specific driver mutations like KRAS and EGFR show a significant association with improved overall survival.
