title: Epithelial-Mesenchymal Expression Phenotype of Primary Melanoma and Matched Metastases and Relationship with Overall Survival.
abstract: E-Cadherin and N-cadherin are important components of epithelial-mesenchymal transition (EMT). The majority of studies on EMT in melanoma have been performed with cultured cell lines or pooled melanoma samples. The goal of our study was to evaluate the expression of E-cadherin and N-cadherin in matched tissue samples from primary and metastatic sites of melanoma and to determine the correlation with survival outcome. We analyzed tissues from 42 melanoma primary lesions and their corresponding metastases, as well as 53 benign nevi, for expression levels of E-cadherin and N-cadherin using immunohistochemical methods. There were heterogenous expression patterns of E- and N-cadherin in both primary and metastatic melanomas. Overall, metastatic tumor showed a decrease in E-cadherin expression and an increase in N-cadherin expression compared to the primary tumor, although the difference did not reach statistical significance (p=0.24 and 0.28 respectively). A switch of membranous expression from E-cadherin to N-cadherin from primary to metastatic melanoma was seen in eight patients (19%). Aberrant E-cadherin expression (defined as negative to weak membranous E-cadherin or positive nuclear E-cadherin expression) was more frequently observed in metastatic than in primary melanomas (p=0.03). Multivariate analysis showed that absence of N-cadherin expression in primary melanomas and the presence of aberrant E-cadherin expression in primary melanomas and metastatic melanomas was associated with a significantly worse overall survival. Our data support the importance of E-cadherin and N-cadherin proteins in melanoma progression and patient survival.
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, U.S.A.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Hematology/Oncology, Dartmouth Hitchcock Medical Center, Lebanon, NH, U.S.A.
authors.forename: Britt M
authors.initials: BM
authors.lastname: Holderness
authors.affiliation: Biostatistics Shared Resource, Geisel School of Medicine at Dartmouth, Lebanon, NH, U.S.A.
authors.forename: Zhongze
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, U.S.A.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Seidel
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, U.S.A.
authors.forename: Jiang
authors.initials: J
authors.lastname: Gui
authors.affiliation: Department of Medicine, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, U.S.A.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, U.S.A. marc.ernstoff@RoswellPark.org.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D015820:Cadherins
keywords: E-cadherin; Epithelial–mesenchymal transition; N-cadherin; melanoma; metastasis