What is a limitation of using PD-L1 expression as a biomarker?

• A. It has no limitations
• B. It is expressed in all tissues equally
• C. Variability in expression and sampling bias
• D. It always perfectly predicts outcomes

Answer: (C)

PD-L1 expression as a biomarker is limited by variability and sampling bias. Tumors are not uniform—PD-L1 levels can differ widely between regions of the same tumor and between primary and metastatic sites. A biopsy captures only a small piece, which may not reflect the overall or current expression in the tumor, leading to sampling bias. In addition, PD-L1 can change over time in response to inflammation, therapy, or tumor evolution, so a single measurement may not represent the present status. Different laboratory assays, antibodies, and scoring thresholds add another layer of inconsistency, and pre-analytic factors like tissue handling can affect results. Because of these factors, PD-L1 status is an imperfect predictor: some patients with high levels do not respond, and some with low or negative levels can respond to PD-1/PD-L1 inhibitors.