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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2017-11, Vol.113, p.93-101
• Main Authors: Lococo, Filippo, Torricelli, Federica, Rossi, Giulio, Alifano, Marco, Damotte, Diane, Rapicetta, Cristian, Tamagnini, Ione, Cavazza, Alberto, Piana, Simonetta, Galeone, Carla, Paci, Massimiliano, Ciarrocchi, Alessia
• Format: Article
• Language: English
• Subjects: Aged; B7-H1 Antigen - biosynthesis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Female; Humans; Immunohistochemistry; Immunotherapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Middle Aged; Multivariate Analysis; Mutation; Mutational burden; PD-L1; Prognosis; Proto-Oncogene Proteins p21(ras) - genetics; Pulmonary carcinosarcoma; Pulmonary sarcomatoid tumor; Survival Analysis
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2017.09.009

•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. Pulmonary 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. Fortythree 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. About 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. PD-L1 expression significantly correlates with overall mutational load and KRAS mutational status in pulmonary sarcomatoid carcinomas.