Analysis of APAF-1 expression in human cutaneous melanoma progression

: APAF‐1 plays a pivotal role in mitochondria‐dependent apoptosis, binding to cytochrome c and favoring activation of caspase‐9. It has been shown that epigenetic silencing of the APAF‐1 gene is a common event in several metastatic melanoma cells in vitro. We determined, by Western blot, variation in the level of expression of APAF‐1 in several human melanoma cell lines and, by immunohistochemistry, in a group of 106 histological samples including benign and malignant melanocytic lesions. We observed APAF‐1 down‐regulation or loss of expression in two metastatic melanoma cell lines, compared to primary melanoma cell lines. The immunohistochemical analysis revealed a significant difference in APAF‐1 staining between nevi and melanomas. In addition, we found a significant negative correlation between APAF‐1 expression level and tumor thickness and between primary melanomas and metastases. We conclude that loss of APAF‐1 expression can be considered as an indicator of malignant transformation in melanoma.