882P Claudin-1 (CLDN1) expression in head and neck squamous cell carcinoma (HNSCC) patients

Recent evidence has shown that the tight junction protein Claudin-1 (CLDN1) is overexpressed in different solid tumors. CLDN1 can be targeted through specific agents to revert its effects. The present work aims to explore CLDN1 expression in a cohort of HNSCC patients (pts). A single center cohort of 100 loco-regionally advanced HNSCC pts included in the BD2Decide project was analyzed [PMID 33107152]. All pts received treatments with curative intent. Primary tumor specimens were profiled for gene expression by Affymetrix ClariomD chips and processed using the Transcriptome Analysis Console Software (ThermoFisher). Normalized and log2 CLDN1 were retrieved from the data matrix and used to analyze: i) data distribution based on anatomical subsites, HPV status, and molecular subtypes assessed by Kruskal-Wallis test; ii) prognostic value having overall survival (OS) as endpoint estimated with Kaplan-Meier method and compared with the log-rank test. Hazard ratios (HR) were estimated with Cox proportional hazard model. The clinical characteristics of the pts cohort are reported in the following table.Table: 882PCharacteristicsN (%)SexM F76 (76) 24 (24)Median age60 years (range 21-80)Primary HNSCC siteOral cavity HPV+ OPC HPV- OPC Hypopharynx Larynx20 (20) 20 (20) 20 (20) 20 (20) 20 (20)StageHPV+ I II III HPV- HNSCCs III IVa/b- 6 (30) 6 (30) 8(40) - 25 (31) 55 (69)CLDN1High (>4.4) Low (<4.4)15 (15) 85 (85)Median follow-up64.44 months [m] (95% CI: 54.24-66.91)Median DFSOverall HPV+ HPV- CLDN1-high CLDN1-low42.79 m (95% CI: 22.5-72.2) 53.91 m (95% CI: 13.09-53.91) 35.53 m (95% CI: 15.43-72.2) 22.9 m (95% CI: 7.96-35.79) 65.1 m (95% CI: 22.5-72.2)Median OSOverall HPV+ HPV- CLDN1-high CLDN1-low94.24 m (95% CI: 59.08-94.24) Not reached 72.2 m (95% CI: 43.88-94.24) 26.2 m (95% CI: 14.31-94.24) Not reached Open table in a new tab CLDN1 expression significantly differed (p=0.0158) among HNSCC primary sites (in decreasing order of expression): hypopharynx, HPV+ oropharynx (OPC), larynx, HPV- OPC, oral cavity. Survival was significantly shorter in pts with high vs low CLDN1 (Table): OS HR=3 (95% CI 1.43-6.28, p=0.0023), DFS HR=2.14 (95% CI 1.11-4.11, p=0.02). CLDN1 expression is heterogeneous in HNSCC pts, and has a prognostic significance. These results may guide pts selection for future clinical studies with anti CLDN1-antobody, which is currently under development.