Virus-positive Merkel Cell Carcinoma Is an Independent Prognostic Group with Distinct Predictive Biomarkers
Recommended Citation
Harms K, Zhao L, Johnson B, Wang X, Carskadon S, Palanisamy N, Rhodes DR, Mannan R, Vo J, Choi JE, Chan MP, Fullen DR, Patel RM, Siddiqui J, Ma VT, Hrycaj S, McLean SA, Hughes TM, Bichakjian CK, Tomlins SA, and Harms PW. Virus-positive Merkel cell carcinoma is an independent prognostic group with distinct predictive biomarkers. Clin Cancer Res 2021.
Document Type
Article
Publication Date
2-5-2021
Publication Title
Clinical cancer research
Abstract
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that can be divided into two classes: virus-positive (VP) MCC, associated with oncogenic Merkel cell polyomavirus (MCPyV); and virus-negative (VN) MCC, associated with photodamage.
EXPERIMENTAL DESIGN: We classified 346 MCC tumors from 300 patients for MCPyV using a combination of IHC, ISH, and qPCR assays. In a subset of tumors, we profiled mutation status and expression of cancer-relevant genes. MCPyV and molecular profiling results were correlated with disease-specific outcomes. Potential prognostic biomarkers were further validated by IHC.
RESULTS: A total of 177 tumors were classified as VP-MCC, 151 tumors were VN-MCC, and 17 tumors were indeterminate. MCPyV positivity in primary tumors was associated with longer disease-specific and recurrence-free survival in univariate analysis, and in multivariate analysis incorporating age, sex, immune status, and stage at presentation. Prioritized oncogene or tumor suppressor mutations were frequent in VN-MCC but rare in VP-MCC.
CONCLUSIONS: MCPyV status is an independent prognostic factor for MCC. Features of the tumor genome, transcriptome, and microenvironment may modify prognosis in a manner specific to viral status. MCPyV status has clinicopathologic significance and allows for identification of additional prognostic subgroups.
Medical Subject Headings
Aged; Aged; 80 and over; Biomarkers; Tumor; Carcinoma; Merkel Cell/diagnosis/etiology/mortality; Cell Transformation; Viral; DNA Copy Number Variations; Disease Susceptibility; Female; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Merkel cell polyomavirus; Middle Aged; Mutation; Neoplasm Staging; Oncogenes; Polyomavirus Infections/complications/virology; Prognosis; Tumor Microenvironment
PubMed ID
33547200
ePublication
ePub ahead of print
Volume
27
Issue
9
First Page
2494
Last Page
2504
