Background: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recom-binant cDNA expression libraries prepared from tumour cells (SEREX), and is still undergoing intensiv...Background: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recom-binant cDNA expression libraries prepared from tumour cells (SEREX), and is still undergoing intensive research. SEREX can define strongly immunogenic tumour antigens that elicit both cellular and humoral immunity. Previous studies have shown that HSP105 is a cancer testis antigen and is overexpressed in various internal malignancies. The expression of HSP105 has not been studied in skin cancers. Objectives: To assess the expression of HSP105 in skin cancers including extramammary Paget disease (EMPD), cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Methods: Samples of EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC (n = 23) were collected from patients treated in our department between January 2002 and December 2004. Western blot and immunohistochemical staining methods were used to investigate the expression of HSP105. Results: Results of Western blot analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression in BCC. Immunohistochemistry results showed that 56%of EMPD, 60%of primary and 100%of metastatic SCC highly expressed HSP105 while only 13%of BCC lesions showed increased staining. Conclusions: EMPD and SCC overexpress HSP105 while BCC does not. Tumours overexpressing HSP105 present ideal candidates for vaccination by HSP105-derived peptides or DNA.展开更多
BACKGROUND: Exposure to ultraviolet light is a major causative factor in melanoma, although the relationship between risk and exposure is complex. We hypothesized that the clinical heterogeneity is explained by geneti...BACKGROUND: Exposure to ultraviolet light is a major causative factor in melanoma, although the relationship between risk and exposure is complex. We hypothesized that the clinical heterogeneity is explained by genetically distinct types of melanoma with different susceptibility to ultraviolet light. METHODS: We compared genome- wide alterations in the number of copies of DNA and mutational status of BRAF and N- RAS in 126 melanomas from four groups in which the degree of exposure to ultraviolet light differs: 30 melanomas from skin with chronic sun- induced damage and 40 melanomas from skin without such damage; 36 melanomas from palms, soles, and subungual (acral) sites; and 20 mucosal melanomas. RESULTS: We found significant differences in the frequencies of regional changes in the number of copies of DNA and mutation frequencies in BRAF among the four groups of melanomas. Samples could be correctly classified into the four groups with 70 percent accuracy on the basis of the changes in the number of copies of genomic DNA. In two- way comparisons, melanomas arising on skin with signs of chronic sun- induced damage and skin without,such signs could be correctly classified with 84 percent accuracy. Acral melanoma could be distinguished from mucosal melanoma with 89 percent accuracy. Eighty- one percent of melanomas on skin without chronic sun- induced damage had mutations in BRAF or N- RAS; the majority of melanomas in the other groups had mutations in neither gene. Melanomas with wild- type BRAF or NRAS frequently had increases in the number of copies of the genes for cyclin- dependent kinase 4 (CDK4) and cyclin D1 (CCND1), downstream components of the RASBRAF pathway. CONCLUSIONS: The genetic alterations identified in melanomas at different sites and with different levels of sun exposure indicate that there are distinct genetic pathways in the development of melanoma and implicate CDK4 and CCND1 as independent oncogenes in melanomas without mutations in BRAF or N- RAS.展开更多
文摘Background: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recom-binant cDNA expression libraries prepared from tumour cells (SEREX), and is still undergoing intensive research. SEREX can define strongly immunogenic tumour antigens that elicit both cellular and humoral immunity. Previous studies have shown that HSP105 is a cancer testis antigen and is overexpressed in various internal malignancies. The expression of HSP105 has not been studied in skin cancers. Objectives: To assess the expression of HSP105 in skin cancers including extramammary Paget disease (EMPD), cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Methods: Samples of EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC (n = 23) were collected from patients treated in our department between January 2002 and December 2004. Western blot and immunohistochemical staining methods were used to investigate the expression of HSP105. Results: Results of Western blot analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression in BCC. Immunohistochemistry results showed that 56%of EMPD, 60%of primary and 100%of metastatic SCC highly expressed HSP105 while only 13%of BCC lesions showed increased staining. Conclusions: EMPD and SCC overexpress HSP105 while BCC does not. Tumours overexpressing HSP105 present ideal candidates for vaccination by HSP105-derived peptides or DNA.
文摘BACKGROUND: Exposure to ultraviolet light is a major causative factor in melanoma, although the relationship between risk and exposure is complex. We hypothesized that the clinical heterogeneity is explained by genetically distinct types of melanoma with different susceptibility to ultraviolet light. METHODS: We compared genome- wide alterations in the number of copies of DNA and mutational status of BRAF and N- RAS in 126 melanomas from four groups in which the degree of exposure to ultraviolet light differs: 30 melanomas from skin with chronic sun- induced damage and 40 melanomas from skin without such damage; 36 melanomas from palms, soles, and subungual (acral) sites; and 20 mucosal melanomas. RESULTS: We found significant differences in the frequencies of regional changes in the number of copies of DNA and mutation frequencies in BRAF among the four groups of melanomas. Samples could be correctly classified into the four groups with 70 percent accuracy on the basis of the changes in the number of copies of genomic DNA. In two- way comparisons, melanomas arising on skin with signs of chronic sun- induced damage and skin without,such signs could be correctly classified with 84 percent accuracy. Acral melanoma could be distinguished from mucosal melanoma with 89 percent accuracy. Eighty- one percent of melanomas on skin without chronic sun- induced damage had mutations in BRAF or N- RAS; the majority of melanomas in the other groups had mutations in neither gene. Melanomas with wild- type BRAF or NRAS frequently had increases in the number of copies of the genes for cyclin- dependent kinase 4 (CDK4) and cyclin D1 (CCND1), downstream components of the RASBRAF pathway. CONCLUSIONS: The genetic alterations identified in melanomas at different sites and with different levels of sun exposure indicate that there are distinct genetic pathways in the development of melanoma and implicate CDK4 and CCND1 as independent oncogenes in melanomas without mutations in BRAF or N- RAS.
