Inter-relationship between PD-L1 expression and clinic-pathological features and driver gene mutations in pulmonary sarcomatoid carcinomas
| Autor: | Diane Damotte, Filippo Lococo, Giulio Rossi, Alessia Ciarrocchi, Massimiliano Paci, Simonetta Piana, Ione Tamagnini, Alberto Cavazza, Cristian Rapicetta, Marco Alifano, Federica Torricelli, Carla Galeone |
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| Rok vydání: | 2017 |
| Předmět: |
PD-L1
Male Pulmonary and Respiratory Medicine Mutational burden Cancer Research Lung Neoplasms Immunohistochemistry Immunotherapy Pulmonary carcinosarcoma Pulmonary sarcomatoid tumor Gene mutation medicine.disease_cause B7-H1 Antigen Proto-Oncogene Proteins p21(ras) 03 medical and health sciences 0302 clinical medicine Settore MED/21 - CHIRURGIA TORACICA Carcinoma Non-Small-Cell Lung Humans Medicine PTEN 030212 general & internal medicine Sarcomatoid carcinoma Survival analysis Aged Univariate analysis biology business.industry Middle Aged Prognosis medicine.disease Survival Analysis Exact test Oncology 030220 oncology & carcinogenesis Multivariate Analysis Mutation Cancer research biology.protein Female KRAS business |
| Zdroj: | Lung Cancer. 113:93-101 |
| ISSN: | 0169-5002 |
| DOI: | 10.1016/j.lungcan.2017.09.009 |
| Popis: | Introduction 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. |
| Databáze: | OpenAIRE |
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