title: Caspases and inhibitor of apoptosis proteins in cutaneous and mucosal melanoma: expression profile and clinicopathologic significance.
abstract: Malignant melanoma is characterized by apoptotic dysfunction, presumably due to abnormal expression of caspases and inhibitor of apoptosis proteins. However, the expression status and clinicopathologic significance of caspases and inhibitor of apoptosis proteins in cutaneous and particularly in mucosal melanomas have not been established. We investigated the expression of the major caspases (CASP3, 6, 7, 8, 9, and 10) and inhibitor of apoptosis proteins (survivin, CIAP1, CIAP2, XIAP, and Livin) by immunohistochemistry in 52 primary cutaneous and 25 mucosal melanomas, and 24 common nevi. Clinicopathologic and prognostic significance was investigated by statistical analysis. Our data showed that the significantly up-regulated inhibitor of apoptosis proteins in primary cutaneous and mucosal melanomas as compared with nevus (P < .01) were survivin, CIAP1, CIAP2, and Livin. Percentage of cases with positive caspase or IAP immunostaining was not significantly different between primary cutaneous and mucosal melanomas or between lower- and higher-stage melanomas (P > .05). Tumor location (cutaneous versus mucosal), stage, and positive cytoplasmic and nuclear survivin staining correlated significantly with prognosis by univariate analysis (P < .01). Multivariate analysis by Cox regression model showed that the most useful prognostic indicators were tumor location (cutaneous versus mucosal, relative risk = 6.021, 95% confidence interval = 2.623 approximately 13.821, P = .000), stage (relative risk = 4.129, 95% confidence interval = 1.817 approximately 9.383, P = .001), and nuclear survivin staining (relative risk = 3.383, 95% confidence interval = 1.137 approximately 10.008, P = .028).
authors.affiliation: Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041 China.
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.forename: Xueqin
authors.initials: X
authors.lastname: Chen
authors.forename: Wentong
authors.initials: W
authors.lastname: Meng
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000032:analysis; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009506:Nevus / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology; D016019:Survival Analysis; D000077022:Survivin; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D020169:Caspases