Human Pathology
Volume 40, Issue 7 , Pages 950-956, July 2009

Caspases and inhibitor of apoptosis proteins in cutaneous and mucosal melanoma: expression profile and clinicopathologic significance☆☆☆

  • Ni Chen, MD, PhD

      Affiliations

    • Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041 China
    • Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041 China
    • ,
  • Jing Gong, MD

      Affiliations

    • Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041 China
    • Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041 China
    • ,
  • Xueqin Chen, MD

      Affiliations

    • Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041 China
    • Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041 China
    • ,
  • Wentong Meng, MD

      Affiliations

    • Laboratory of Stem Cell Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041 China
    • ,
  • Ying Huang, MD

      Affiliations

    • Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041 China
    • Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041 China
    • ,
  • Fang Zhao, MD

      Affiliations

    • Department of Pathology, Haartman Institute, Haartmaninkatu 3, PL 21, 00014, University of Helsinki, Helsinki, Finland
    • ,
  • Lin Wang, MD, PhD

      Affiliations

    • Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
    • ,
  • Qiao Zhou, MD, PhD

      Affiliations

    • Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041 China
    • Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041 China
    • Corresponding Author InformationCorresponding author.

Received 2 August 2008; received in revised form 2 December 2008; accepted 3 December 2008. published online 09 March 2009.

Summary 

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∼13.821, P = .000), stage (relative risk = 4.129, 95% confidence interval = 1.817∼9.383, P = .001), and nuclear survivin staining (relative risk = 3.383, 95% confidence interval = 1.137∼10.008, P = .028).

Keywords: Caspase, Expression, IAP, Melanoma, Prognosis

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☆ Supported by grants to Dr Zhou from the Natural Science Foundation of China (30570692, 30221001, 30871383) and the Ministry of Education PhD Program Fund of China (20060610053), and to Dr. N Chen (30800637). Dr Meng was supported by the National Basic Research Program of China (2007CB947802).

☆☆ Dr Ni Chen and Dr Jing Gong contributed equally to this project.

PII: S0046-8177(08)00573-X

doi:10.1016/j.humpath.2008.12.001

Human Pathology
Volume 40, Issue 7 , Pages 950-956, July 2009

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