Research paperInter-relationship between PD-L1 expression and clinic-pathological features and driver gene mutations in pulmonary sarcomatoid carcinomas

- Pulmonary Sarcomatoid Carcinoma (PSC) is a rare and aggressive subset of NSCLC.
- PCS presented a high mutational burden provides a rationale for immunotherapy.
- We herein show a significant PD-L1 expression (>10% of tumor cells) in 25% of PSCs.
- We found a strong association between PD-L1 expression and KRAS mutations.
- We distinct 2 immunological subtypes in PCS: PD-L1+/KRAS-mut vs PD-L1-/KRAS-wild.

IntroductionPulmonary Sarcomatoid Carcinoma (PSC) is a rare subset of NSCLC, associated with worse prognosis and resistant to platinum-based regimens. Recent investigations have shown high levels of PD-L1 expression in PSC, providing a rationale for the potential use of immunotherapy. In this study, we investigated whether the PD-L1 expression was related to clinico-pathologic and molecular characteristics.Materials and methodsFortythree surgically-resected PSCs were selected from 2006 to 2014 and clinical information retrieved. PD-L1 expression was analyzed by immunohistochemistry and correlated with the clinic-pathologic features and driver gene mutations analyzed by Next-Generation-Sequencing. Correlation of clinical, pathological and genetic variants with PD-L1 expression positivity were tested by Fisher's exact test analysis.ResultsAbout 25% of PSCs showed a significant expression of PD-L1 (positive staining defined as staining in ≥10% of tumor cells). PD-L1 expression was associated with aggressive pathological features of PSCs including N2-involvement (PD-L1 positive in 83.3% of N2-PSCs vs in 16.2% of N0/N1-PSCs, p = 0.003) and presence of either local (p = 0.038) and distant metastases (p = 0.022). Furthermore, PD-L1 expression was significantly associated with the overall mutational load of the tumors (PD-L1 positivity only in PSCs with at least one mutational event) and in particular with the presence of KRAS mutation (PD-L1 positive in 44.4% of KRAS-Mut PSCs vs 12.0% in KRAS-Wild PSCs). The correlation between PD-L1 expression and KRAS-mutation were found at univariate analysis (p = 0.031), even considering PD-L1 as a continuous variable (p = 0.018), and confirmed at multivariate analysis (p = 0.035). The mutational status of the other genes explored in the NGS-panel (EGFR, APC, PTEN, PIK3CA, TP53 and STK11) did not correlate with PD-L1 expression.ConclusionsPD-L1 expression significantly correlates with overall mutational load and KRAS mutational status in pulmonary sarcomatoid carcinomas.