Title: Merkel Cell Carcinoma Patients Presenting Without a Primary Lesion Have Elevated Markers of Immunity, Higher Tumor Mutation Burden, and Improved Survival.
Authors: Vandeven, Natalie; Lewis, Christopher W; Makarov, Vladimir; Riaz, Nadeem; Paulson, Kelly G; Hippe, Daniel; Bestick, Amy; Doumani, Ryan; Marx, Tessa; Takagishi, Seesha; Chan, Timothy A; Choi, Jaehyuk; Nghiem, Paul
Published In Clin Cancer Res, (2018 02 15)
Abstract: Purpose: Patients presenting with nodal Merkel cell carcinoma without an identifiable (unknown) primary lesion (MCC-UP) are nearly twice as likely to survive compared with similarly staged patients with known primary lesions (MCC-KP). The basis of this previously reported finding is unclear.Experimental Design: Survival analyses and markers of immunity were evaluated in 123 patients with advanced MCC. Whole-exome sequence data were analyzed from 16 tumors.Results: As in prior studies, patients with nodal MCC-UP had strikingly improved MCC-specific survival as compared with MCC-KP patients (HR, 0.297; P < 0.001). Surprisingly, patients presenting with distant metastatic MCC-UP also had significantly improved survival (HR, 0.296; P = 0.038). None of the 72 patients with MCC-UP were immunosuppressed as compared to 12 of the 51 (24%) patients with MCC-KP (P < 0.001). Merkel polyomavirus oncoprotein antibody median titer was higher in MCC-UP patients (26,229) than MCC-KP patients (3,492; P < 0.001). In addition, the median number of nonsynonymous exome mutations in MCC-UP tumors (688 mutations) was markedly higher than MCC-KP tumors (10 mutations, P = 0.016).Conclusions: This is the first study to our knowledge to explore potential underlying immune-mediated mechanisms of MCC-UP presentation. In this cohort, MCC-UP patients were never immune suppressed, had higher oncoprotein antibody titers, and higher tumor mutational burdens. In addition, we show that nodal tumors identified in MCC-UP patients did indeed arise from primary skin lesions as they contained abundant UV-signature mutations. These findings suggest that stronger underlying immunity against MCC contributes to primary lesion elimination and improved survival. Clin Cancer Res; 24(4); 963-71. ©2017 AACR.
PubMed ID: 29246939
MeSH Terms: Aged; Biomarkers, Tumor/genetics; Biomarkers, Tumor/immunology*; Biomarkers, Tumor/metabolism; Carcinoma, Merkel Cell/genetics; Carcinoma, Merkel Cell/immunology*; Carcinoma, Merkel Cell/therapy; Female; Humans; Immunotherapy/methods; Lymphatic Metastasis; Male; Middle Aged; Mutation*; Skin Neoplasms/genetics; Skin Neoplasms/immunology*; Skin Neoplasms/therapy; Skin/immunology*; Skin/metabolism; Skin/pathology; Survival Analysis; Tumor Burden/genetics; Tumor Burden/immunology*; Whole Exome Sequencing