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Lower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis
- Source :
- Human Pathology. 48:1-8
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Merkel 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.
- Subjects :
- Male
0301 basic medicine
Pathology
medicine.medical_specialty
Skin Neoplasms
Immunoglobulins
Merkel cell polyomavirus
Kaplan-Meier Estimate
Real-Time Polymerase Chain Reaction
Disease-Free Survival
Pathology and Forensic Medicine
03 medical and health sciences
Cytokeratin
0302 clinical medicine
Biomarkers, Tumor
medicine
Adenocarcinoma of the lung
Humans
Aged
Proportional Hazards Models
Polyomavirus Infections
biology
Merkel cell carcinoma
Cell adhesion molecule
Myelin and Lymphocyte-Associated Proteolipid Proteins
Cell Adhesion Molecule-1
Cancer
Middle Aged
Prognosis
medicine.disease
biology.organism_classification
Immunohistochemistry
Carcinoma, Merkel Cell
Tumor Virus Infections
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Skin cancer
Merkel cell
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 00468177
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Human Pathology
- Accession number :
- edsair.doi.dedup.....290a89e51dabd43204c1f22110b9b85c