Merkel Cell Carcinoma Patients Presenting Without a Primary Lesion Have Elevated Markers of Immunity, Higher Tumor Mutation Burden, and Improved Survival
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- Natalie Vandeven
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Christopher W. Lewis
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Vladimir Makarov
- 2Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
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- Nadeem Riaz
- 2Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
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- Kelly G. Paulson
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Daniel Hippe
- 5Department of Radiology, University of Washington, Seattle, Washington.
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- Amy Bestick
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Ryan Doumani
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Tessa Marx
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Seesha Takagishi
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
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- Timothy A. Chan
- 2Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
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- Jaehyuk Choi
- 6Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
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- Paul Nghiem
- 1Department of Medicine (Dermatology), University of Washington, Seattle, Washington.
抄録
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p> <jats:p>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.</jats:p> <jats:p>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).</jats:p> <jats:p>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.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 24 (4), 963-971, 2018-02-14
American Association for Cancer Research (AACR)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1364233269285882752
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- ISSN
- 15573265
- 10780432
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- データソース種別
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- Crossref