Concordance of programmed death-ligand 1 expression assessments determined via two immunohistochemical tests and the polymerase chain reaction method

Abstract

BACKGROUND

We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1 (PDCD1 LG1) is a promising new marker of programmed death-ligand 1 (PD-L1) expression that correlates with both breast cancer (BC) clinicopathological characteristics and tumor sensitivity to chemotherapy. However, the concordance of PDCD1 LG1 expression scoring with immunohistochemical (IHC) tests approved for clinical use and with the polymerase chain reaction (PCR) method has not been previously studied.

AIM

To evaluate the concordance of methods for assessing PD-L1 expression, IHC tests with anti-PD-L1 (PDCD1 LG1) and anti-PD-L1 (SP142) antibodies and PCR.

METHODS

This prospective single-center observational cohort study included 148 patients with BC. PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1 (PDCD1 LG1) and anti-PD-L1 (SP142) antibodies and by PCR. The concordance of PD-L1 scores between tests was assessed with positive percentage agreement (PPA) and negative percentage agreement (NPA). The strength of the agreement between the methods was calculated via the Cohen kappa index. P < 0.05 was considered statistically significant.

RESULTS

Regardless of the method used to assess marker expression, PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status, human epidermal growth factor receptor-2-positive (HER2+) status, luminal B HER+ BC, nonluminal HER+ BC and triple-negative BC. PPA and NPA were 38.3% and 70.4%, respectively, for PD-L1 (PDCD1 LG1) and PD-L1 (SP142); 26.3% and 63.3%, respectively, for PD-L1 (PDCD1 LG1) and PD-L1 (PCR); and 36.5% and 74.4%, respectively, for PD-L1 (SP142) and PD-L1 (PCR). Cohen's kappa index for PD-L1 (PDCD1 LG1) and PD-L1 (SP142) was 0.385 (95%CI: 0.304–0.466), that for PD-L1 (PDCD1 LG1) and PD-L1 (PCR) was 0.207 (95%CI: 0.127–0.287), and that for PD-L1 (SP142) and PD-L1 (PCR) was 0.389 (95%CI: 0.309–0.469).

CONCLUSION

Thus, all three markers of PD-L1 expression are associated with the characteristics of aggressive BC, demonstrating moderate concordance between the tests.

Keywords: Breast cancer; Cohen kappa index; Negative percentage agreement; Positive percentage agreement; Programmed death-ligand 1; Programmed cell death protein 1 ligand 1

Core Tip: We determined the expression of programmed cell death ligand 1 in immune cells using immunohistochemistry with antibodies against programmed cell death protein 1 ligand 1 (PDCD1 LG1) and SP142 and polymerase chain reaction (PCR) and then examined the agreement between the results of three assays in patients with breast cancer (BC). All three tests were positively correlated with estrogen receptor-negative status, human epidermal growth factor receptor-2-positive (HER2+) status, and luminal B HER+, nonluminal HER+, and triple-negative BCs. Cohen's kappa index was 0.385 for PDCD1 LG1 and SP142 and 0.389 for SP142 and programmed death-ligand 1 (PCR), which is considered moderate agreement between the markers.