title: High expression of cytoplasmic phosphorylated CSE1L in malignant melanoma but not in benign nevi: phosphorylated CSE1L for the discrimination between melanoma and benign nevi.
abstract: Melanoma is difficult to treat when it has metastasized. Discrimination between melanoma and benign nevi in melanocytic lesions is crucial for identifying melanomas and consequently improving melanoma treatment and prognosis. The chromosome segregation 1-like (CSE1L) protein has been implicated in cancer progression and is regulated by phosphorylation by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, a critical pathway in melanoma progression. We studied phosphorylated CSE1L expression in human melanoma and benign nevi specimens. Immunohistochemistry with tissue microarray using antibody against phosphorylated CSE1L showed that melanomas exhibited considerable staining for phosphorylated CSE1L (100%, 34/34), whereas the benign nevi showed only faint staining (0%, 0/34). Melanomas mainly exhibited cytoplasmic phospho-CSE1L distribution, whereas the benign nevi mainly exhibited nuclear phospho-CSE1L distribution. Moreover, immunohistochemistry with anti-CSE1L antibody revealed that CSE1L mainly exhibited cytoplasmic/nuclear distribution and nuclear distribution was the dominant. Immunofluorescence with B16F10 melanoma cells showed cytoplasmic distribution of phospho-CSE1L and nuclear distribution of CSE1L. Our results indicated that nuclear CSE1L is mainly non-phosphorylated CSE1L and is involved in gene regulation and cytoplasmic CSE1L is mainly phosphorylated CSE1L and is involved in cytoplasmic signaling regulation in melanocytic tumorigenesis. Furthermore, immunohistochemical analysis of cytoplasmic phospho-CSE1L may aid in the diagnosis of melanoma.
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University New Taipei City, Taiwan ; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Szu-Ying
authors.initials: SY
authors.lastname: Chin
authors.affiliation: Department of Pathology, Changhua Christian Hospital Changhua, Taiwan ; School of Medicine, Chung Shan Medical University Taichung, Taiwan.
authors.forename: Pei-Ru
authors.initials: PR
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University New Taipei City, Taiwan ; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Department of Pathology, Changhua Christian Hospital Changhua, Taiwan ; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management Miaoli, Taiwan.
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Yeh
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University New Taipei City, Taiwan ; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Woan-Ruoh
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Shing-Chuan
authors.initials: SC
authors.lastname: Shen
authors.affiliation: Department of Pathology, Changhua Christian Hospital Changhua, Taiwan ; School of Medicine, Chung Shan Medical University Taichung, Taiwan.
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University New Taipei City, Taiwan.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University New Taipei City, Taiwan ; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Jonathan Te-Peng
authors.initials: JT
authors.lastname: Tseng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D029563:Cellular Apoptosis Susceptibility Protein / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009506:Nevus / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein
keywords: CSE1L; cytoplasmic; melanoma; nuclear; phospho-CSE1L; phosphorylation