Lower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis.
AffiliationDivision of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, 683-8503, Japan
MetadataShow full item record
AbstractMerkel cell carcinoma (MCC) is a clinically aggressive neuroendocrine skin cancer; 80% of the cases are associated with the Merkel cell polyomavirus (MCPyV). We previously reported that MCPyV-negative MCCs have more irregular nuclei with abundant cytoplasm and significantly unfavorable outcomes than do MCPyV-positive MCCs. These results suggest that some cell adhesion or structural stabilization molecules are differently expressed depending on MCPyV infection status. Thus, we investigated the association of prognosis or MCPyV infection status in MCCs with cell adhesion molecule 1 (CADM1)/differentially expressed in adenocarcinoma of the lung protein 1 (DAL-1)/membrane protein, palmitoylated 3 (MPP3) tripartite complex and mal T-cell differentiation protein (MAL) expression, which play important roles in cell adhesion and oncogenesis and are related to cancer outcomes in various malignancies, to elucidate the role of these molecules. We analyzed the pathological and molecular characteristics of 26 MCPyV-positive and 15 MCPyV-negative MCCs. Univariate Cox regression analysis showed that advanced age (hazard ratio [HR], 8.249; P = .007) and high CADM1 expression (HR, 5.214; P = .012) were significantly unfavorable overall survival parameters, whereas MCPyV infection (HR, 0.043, P < .001) and lower MAL expression (HR, 0.273; P = .018) were significantly favorable. On multivariate analysis, only MCPyV infection was significantly favorable for overall survival (HR, 0.04; P = .005). Hypermethylation of CADM1, DAL-1, and MAL promoters was detected in 1 of 18, 15 of 27, and 1 of 13 cases, respectively. Double immunostaining for cytokeratin 20 and CADM1, DAL-1, or MAL showed that nonneoplastic Merkel cells expressed DAL-1 and MAL but not CADM1. This study revealed that MCPyV-negative MCCs significantly expressed higher CADM1 and lower MAL than MCPyV-positive MCCs; these expression levels were markedly related to unfavorable outcomes. These data will give us important insights to develop novel molecular target therapies for MCCs.
CitationLower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis. 2016, 48:1-8 Hum Pathol
- Immunoglobulin expressions are only associated with MCPyV-positive Merkel cell carcinomas but not with MCPyV-negative ones: comparison of prognosis.
- Authors: Murakami I, Takata K, Matsushita M, Nonaka D, Iwasaki T, Kuwamoto S, Kato M, Mohri T, Nagata K, Kitamura Y, Yoshino T, Hayashi K
- Issue date: 2014 Dec
- Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor microenvironment is associated with Merkel cell polyomavirus status and prognosis in Merkel cell carcinoma.
- Authors: Wardhani LO, Matsushita M, Iwasaki T, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K
- Issue date: 2019 Feb
- Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.
- Authors: Iwasaki T, Matsushita M, Nonaka D, Kuwamoto S, Kato M, Murakami I, Nagata K, Nakajima H, Sano S, Hayashi K
- Issue date: 2015 Feb
- Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma.
- Authors: Sihto H, Kukko H, Koljonen V, Sankila R, Böhling T, Joensuu H
- Issue date: 2011 Jul 15
- Usefulness of significant morphologic characteristics in distinguishing between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinomas.
- Authors: Iwasaki T, Matsushita M, Kuwamoto S, Kato M, Murakami I, Higaki-Mori H, Nakajima H, Sano S, Hayashi K
- Issue date: 2013 Sep