Stratification of Prognosis in Pulmonary Pleomorphic Carcinoma Based on Integrated PD-L1 and Multiparametric Biomarker Analysis.

BACKGROUND/

OBJECTIVES

Published data on reliable prognostic biomarkers for pulmonary pleomorphic carcinoma (PPC), a rare, aggressive subtype of non-small cell lung cancer, are limited. Programmed death-ligand 1 (PD-L1) has been studied; however, the prognostic impact of other immunoregulatory molecules, such as CD73, CD155, and Ki-67 and their combined expression profiles, remains unclear.

METHODS

We retrospectively analyzed data of 47 patients who had undergone macroscopic complete resection of PPC between January 2000 and December 2022. Immunohistochemistry for PD-L1, CD73, CD155, and Ki-67 was performed. Cut-off values were determined by receiver operating characteristic analysis for cancer-specific death. The primary endpoint was the association between each biomarker and overall survival (OS) or cancer-specific survival (CSS). The secondary endpoint was the prognostic value of combined biomarker profiles, particularly PD-L1 with CD73, CD155, or Ki-67.

RESULTS

At a positivity threshold of 1%, the positivity rates were 70.2% for PD-L1, 89.4% for CD73, 91.5% for CD155, and 83.0% for Ki-67. There were no statistically significant differences in OS or CSS between groups with high expression and those with low expression for any single marker. Secondary endpoint analysis showed that low PD-L1 and low CD73 predicted significantly poorer OS (p = 0.046) and low PD-L1 and low Ki-67 predicted significantly poorer CSS (p = 0.039) compared with other combinations.

CONCLUSIONS

Primary endpoint analyses showed no statistically significant association between any single marker and prognosis in PPC. In contrast, secondary endpoint findings indicated that concurrent low PD-L1 with either low CD73 or low Ki-67 identified subsets with significantly poorer outcomes. The present findings provide a basis for further investigation of biomarker combinations for prognostic assessment in this rare lung cancer. Because of the limited sample size, these findings are exploratory and require validation in larger independent cohorts.