A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma |
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Authors: | Soledad Iseas,Mariano Golubicki,Juan Robbio,Gonzalo Ruiz,Florencia Guerra,Javier Mariani,Ruben Salanova,Ana Cabanne,Martin Eleta,Joaquin V. Gonzalez,Jorge Basiletti,Marí a Alejandra Picconi,Guillermo Masciangioli,Marcela Carballido,Enrique Roca,Guillermo Mendez,Mariana Coraglio,Martin C. Abba |
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Abstract: | Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk Human papillomavirus (HPV) infection. Despite improved outcomes in non-metastatic ASCC, definitive chemoradiotherapy constitutes the standard treatment for localized disease. Evidences for predictive and prognostic biomarkers are limited. Here, we performed a viral, immune, and mutational characterization of 79 non-metastatic ASCC patients with complete definitive chemoradiotherapy. HPV-16 was detected in 91% of positive cases in single infections (78%) or in coinfections with multiple genotypes (22%). Fifty-four percent of non-metastatic ASCC cases displayed mutations affecting cancer driver genes such as PIK3CA (21% of cases), TP53 (15%), FBXW7 (9%), and APC (6%). PD-L1 expression was detected in 57% of non-metastatic ASCC. Increased PD-L1 positive cases (67%) were detected in patients with complete response compared with non-complete response to treatment (37%) (p = 0.021). Furthermore, patients with PD-L1 positive tumors were significantly associated with better disease-free survival (DFS) and overall survival (OS) compared with patients with PD-L1 negative tumors (p = 0.006 and p = 0.002, respectively). PD-L1 expression strongly impacts CR rate and survival of non-metastatic ASCC patients after standard definitive chemoradiotherapy. PD-L1 expression could be used to stratify good versus poor responders avoiding the associated morbidity with abdominal perineal resection. |
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Keywords: | ASCC HIV HPV TIL PD-L1 HER2/NEU Targeted DNA sequencing |
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