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

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

Lococo F, Torricelli F, Rossi G, Alifano M, Damotte D, Rapicetta C, Tamagnini I, Cavazza A, Piana S, Galeone C, Paci M, Ciarrocchi A.

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

Lung Cancer. 2017 Nov;113:93-101. doi: 10.1016/j.lungcan.2017.09.009. Epub 2017 Sep 18.

NTRODUCTION:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

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