EP1.04-37 Biomarkers in Non-Small Cell Lung Cancer: Expression of PD-L1 Protein and p16 in Squamous Cell Carcinoma Histologic Subtype

Abstract

Squamous cell carcinoma (SCC), 30% of Non-Small Cell Lung Cancer (NSCLC), cigarette is its mayor etiology. >50% NSCLC are diagnosed in advanced/stage, 10–15%EIIIB, 40%E-IV. In terms of survival, NSCLC is heterogeneous and variable. Survival at 5 years is <15%, treatment is not curative. In cancer, the evasion of the immune system and the uncontrolled tumor proliferation is important. The programmed-cell-death-ligand (PD-L1) is a lymphocyteT protein. The union PD-1/PD-L1 inhibits the lymphocyteT’s activity. Overexpression of PD/L1 in CD8+lymphocytes inhibits apoptosis, reduces survival. In NSCLC, PD-L1 is a predictor of successful immunotherapy. Inhibition PD:PD-L1 is an effective antitumoral therapy. The p16INK4a intervenes in pulmonary carcinogenesis, localized in chromosome 9p21(locus CDKN2A), its codes suppressor/tumoral proteins:p16INK4a-p14ARF. P16 inhibits D1-dependent quinases4-6(CDK4/6,ciclinaD1) which regulate the retinoblastoma protein through phosphorylation. Dysfunctional p16 inactivates Rb through hyperphosphorilation and progression of the cell cycle. Its expression contributes to the therapeutic response and to survival in NSCLC. We describe the clinical, pathological and survival characteristics in SCC based in expression of PD-L1/p16. Descriptive study, 24 patients with SCC, 2009–2013. PD–L1 studied with antibody 22C3 pharmDxkit(Agilent,Santa-Clara,CA,USA) in Autostainer Link/48DAKO®with murine monoclonal antibody(Clone/E6H4™) in BenchMark/Autostainer(Ventana®). PD-L1 was classified with TPS(Tumor/Proportion/Score), high expression TPS>50%, low expression TPS1-49%, or negative TPS=0%. P16(+) with expression >70% in nuclei, tumoral membranes. STATAv.14®, ShapiroWilk, Chi squared, Fisher, t-Student or U/Mann/Whitney were used. Survival with Kaplan-Meier. Age 67±14, 63%men. 54% of smokers, 7% had COPD. E-IV54%, E-IIIA25%, E-IIIB13%, E-IIB y E-IIA4%. PD-L1(+) more in smokers (85%) p=0.001. Treatment: palliative/care (25%), chemotherapy/surgery (17%); chemotherapy/radiotherapy/surgery (12%); radiotherapy/surgery(8%), only surgery(4%). PD-L1, high-expression survival 33m, low expression/negative 66m (log-rank test p=0.0041), Figure1: p16(+) in 10(41.6%), survival 36.2m, p16(-) survival 66.8m, p16/PD-L1(-) survival 66.8m, p16/PD-L1(+) survival 36.2m. SCC with PD-L1 TPS≥50%, p16(+), smokers with high/tumor/burden had lower survival rates. Immunotherapy against programmed cell death (PD-1) is a promising alternative impacting survival in advanced/metastatic NSCLC.