Virus-positive Merkel Cell Carcinoma Is an Independent Prognostic Group with Distinct Predictive Biomarkers

被引：64

作者：

Harms, Kelly L. ^{[1
,2
]}

Zhao, Lili ^{[3
]}

Johnson, Bryan ^{[4
]}

Wang, Xiaoming ^{[5
,6
]}

Carskadon, Shannon ^{[7
]}

Palanisamy, Nallasivam ^{[7
]}

Rhodes, Daniel R. ^{[4
]}

Mannan, Rahul ^{[5
,6
]}

Vo, Josh N. ^{[5
,6
]}

Choi, Jae Eun ^{[6
]}

Chan, May P. ^{[1
,6
]}

Fullen, Douglas R. ^{[1
,6
]}

Patel, Rajiv M. ^{[1
,6
]}

Siddiqui, Javed ^{[5
,6
]}

Ma, Vincent T. ^{[2
,8
]}

Hrycaj, Steven ^{[6
]}

McLean, Scott A. ^{[9
]}

Hughes, Tasha M. ^{[10
]}

Bichakjian, Christopher K. ^{[1
,2
]}

Tomlins, Scott A. ^{[4
,5
,6
]}

Harms, Paul W. ^{[1
,2
,5
,6
]}

机构：

[1] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[4] Strata Oncol, Ann Arbor, MI USA

[5] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[7] Henry Ford Hlth Syst, Dept Urol, Vattikuti Urol Inst, Detroit, MI USA

[8] Univ Michigan, Div Hematol & Oncol, Tepartment Internal Med, Ann Arbor, MI 48109 USA

[9] Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA

[10] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

来源：

CLINICAL CANCER RESEARCH | 2021年 / 27卷 / 09期

关键词：

LARGE T-ANTIGEN; POLYOMAVIRUS INFECTION; EXPRESSION; MUTATIONS; SURVIVAL; AMPLIFICATION; INFILTRATION; INTEGRATION; PROFILES;

D O I：

10.1158/1078-0432.CCR-20-0864

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 diseasespecific 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. TP53 mutation developed with recurrence in one VP-MCC case. Importantly, for the first time we find that VP-MCC and VN-MCCdisplay distinct sets of prognostic molecular biomarkers. For VP-MCC, shorter survival was associated with decreased expression of immune markers including granzyme and IDO1. For VN-MCC, shorter survival correlated with high expression of several genes including UBE2C. 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.

引用

页码：2494 / 2504

页数：11

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