Αρχειοθήκη ιστολογίου

Παρασκευή 15 Δεκεμβρίου 2017

Merkel cell carcinoma patients presenting without a primary lesion have elevated markers of immunity, higher tumor mutation burden and improved survival

Purpose: Patients presenting with nodal Merkel cell carcinoma without an identifiable (unknown) primary lesion (MCC-UP) are nearly twice as likely to survive compared to 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 was analyzed from 16 tumors. Results: As in prior studies, patients with nodal MCC-UP had strikingly improved MCC-specific survival as compared to 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). Additionally, 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. Additionally, 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.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kzkwb5

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