피부 멜라닌세포질환에서 악성 진행에 따른 세포자멸사 관련 단백들(Apaf-1, Caspase-9, Bcl-2, p53, and Survivin)의 변화
Alteration of Apoptosis-Related Proteins (Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesions
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Background: Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions. Methods: We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus. Results: The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01). Conclusions: The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.
Abstract
Background: Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions. Methods: We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus. Results: The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01). Conclusions: The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.
참고문헌 (21)
- Hussein MR, "Apoptosis and melanoma: molecular mechanisms", J Pathol, 199, pp.275~288 (2003)
- Schmitt CA, "Apoptosis and therapy", J Pathol, 187, pp.127~137 (1999)
- Helmbach H, "Drug-resistance in human melanoma", Int J Cancer, 93, pp.617~622 (2001)
- Baldi A, "Analysis of APAF-1 expression in human cutaneous melanoma progression", Exp Dermatol, 13, pp.93~97 (2004)
- Niedojadlo K, "Apaf-1 expression in human cutaneous melanoma progression and in pigmented nevi", Pigment Cell Res, 19, pp.43~50 (2006)
- Soengas MS, "Apaf-1 expression in malignant melanoma", Cell Death Differ, 13, pp.352~353 (2006)
- Mustika R, "Decreased expression of Apaf-1 with progression of melanoma", Pigment Cell Res, 18, pp.59~62 (2005)
- Dai DL, "Reduced Apaf-1 expression in human cutaneous melanomas", Br J Cancer, 91, pp.1089~1095 (2004)
- Raj D, "Survivin repression by p53, Rb and E2F2 in normal human melanocytes", Carcinogenesis, 29, pp.194~201 (2008)
- Ding Y, "Nuclear expression of the antiapoptotic protein survivin in malignant melanoma", Cancer, 106, pp.1123~1129 (2006)
- Takeuchi H, "Survivin expression by metastatic melanoma predicts poor disease outcome in patients receiving adjuvant polyvalent vaccine", Int J Cancer, 117, pp.1032~1038 (2005)
- Florell SR, "Proliferation, apoptosis, and survivin expression in a spectrum of melanocytic nevi", J Cutan Pathol, 32, pp.45~49 (2005)
- Gradilone A, "Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from melanoma patients", J Clin Oncol, 21, pp.306~312 (2003)
- Sträter J, "Expression and prognostic significance of APAF-1, caspase-8 and caspase-9 in stage II", III colon carcinoma: caspase-8 and caspase-9 is associated with poor prognosis, 2010, pp.127, 873~880
- Tchernev G, "Downregulation of cell cycle modulators p21, p27, p53, Rb and proapoptotic Bcl-2-related proteins Bax and Bak in cutaneous melanoma is associated with worse patient prognosis: preliminary findings", J Cutan Pathol, 34, pp.247~256 (2007)
- Ibrahim N, "Molecular pathogenesis of cutaneous melanocytic neoplasms", Annu Rev Pathol, 4, pp.551~579 (2009)
- Tron VA, "Immunohistochemical analysis of Bcl-2 protein regulation in cutaneous melanoma", Am J Pathol, 146, pp.643~650 (1995)
- Collins KA, "Intercellular adhesion molecule 1 (ICAM-1) and bcl-2 are differentially expressed in early evolving malignant melanoma", Am J Dermatopathol, 17, pp.429~438 (1995)
- van den Oord JJ, "Bcl-2 expression in human melanocytes and melanocytic tumors", Am J Pathol, 145, pp.294~300 (1994)
- Ilmonen S, "Ki-67, Bcl-2 and p53 expression in primary and metastatic melanoma", Melanoma Res, 15, pp.375~381 (2005)
- McGregor JM, "p53 immunoreactivity in human malignant melanoma and dysplastic naevi", Br J Dermatol, 128, pp.606~611 (1993)
