title: Expression of cell cycle inhibitor p27Kip1 and its inactivator Jab1 in melanocytic lesions.
abstract: Decreased expression of p27 (a cyclin-dependent kinase inhibitor) is an adverse prognostic marker in a diverse array of human cancers. The purpose of this study was to investigate the expression of p27 and Jab1 (a protein involved in p27 degradation) in melanocytic lesions, and to identify their possible participation in melanoma progression. A tissue microarray was constructed using formalin-fixed, paraffin-embedded archival tissue blocks of 94 melanocytic lesions including 19 benign nevi, 21 dysplastic nevi, 23 melanomas, and 31 metastatic melanomas. The expression of p27 and Jab1 was evaluated by immunohistochemistry. The association between p27, Jab1, and clinicopathological parameters was analyzed using chi2 and Fisher's exact tests. Nonparametric Pearson's rank correlation was applied to evaluate the relationship between p27 and Jab1 expression. p27 was expressed in 15 (88%) nevi, 18 (95%) dysplastic nevi, 11 (50%) melanomas, and only in four (13%) of the metastatic melanomas (P<0.001). Jab1 was expressed in 14 (82%) standard nevi, 18 (95%) dysplastic nevi, 17 (77%) melanomas, and 16 (53%) of the metastatic melanomas (P<0.01). In metastatic melanomas, there was a negative correlation between p27 and Jab1 expression (r=-0.166). The low levels of p27 in primary and metastatic melanoma cases may explain the high proliferation rate of such lesions. Also, the relative high expression of Jab1 in metastatic melanoma, associated with low levels of p27, suggests that Jab1 may be involved in survival and proliferation of metastatic melanoma cells.
authors.affiliation: Department of Pathology, University of Texas, Houston, TX, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Ivan
authors.forename: A Hafeez
authors.initials: AH
authors.lastname: Diwan
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
mesh_terms: D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000096:biosynthesis*; D016009:Chi-Square Distribution; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008544:Melanocytes / Q000737:chemistry / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D009506:Nevus / Q000378:metabolism / Q000473:pathology*; D010447:Peptide Hydrolases; D011379:Prognosis; D012189:Retrospective Studies; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: C436291:CDKN1B protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex