CD274 and neoplasm: However, classification and stratification of patients based on manual IHC methods may not always be reproducible, as a number of factors can create challenges for pathologists when scoring PD-L1 on TCs, such as heterogenous PD-L1 expression within the tumor microenvironment and variable staining patterns in different cellular compartments (e.g. membrane vs. cytoplasmic staining), potentially leading to substantial inter-observer variability6,15,17,30,31.