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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Dermatofibrosarcoma protuberans with fibrosarcomatous areas. Molecular abnormalities of the p53 pathway in fibrosarcomatous transformation of dermatofibrosarcoma protuberans.

Fibrosarcomatous (FS) change in a rare, but well-known phenomenon encountered in dermatofibrosarcoma protuberans (DFSP), and an increased chance in an adverse outcome has been suggested in patients with DFSP having FS areas (DFSP-FS). As altered p53 pathway has been suggested as having a potential role in tumour progression, we analysed the p53 gene and p53 protein together with the p53-related protein mdm2 and p21Waf1 in 5 cases of DFSP-FS and 13 of DFSP to ascertain whether the p53 pathway correlates to the fibrosarcomatous transformation of DFSP. Three of the five DFSP-FSs overexpressed p53 protein immunohistochemically, and one of them had a "missense" mutation of the p53 gene without immunohistochemical overexpression of mdm2 or p21Waf1. The other two DFSP-FSs with p53 overexpression demonstrated increased labelling indices of both mdm2 and p21Waf1. The three DFSP-FS patients with overexpression of p53 protein had frequent local recurrences, ranging from 3 to 5 in number with increasingly short intervals (mean 4.5 years), while one of the other two had no recurrences and the other, only one. None of the 13 DFSPs showed any alterations in the p53 gene or overexpressions of p53, mdm2 and p21Waf1, except for one DFSP having a "silent" mutation of the p53 gene. Three DFSPs had local recurrences once or twice with longer intervals to recurrence (mean 10.3 years). Although the number of cases examined is limited, the results suggest that alterations in the p53 pathway, such as overexpression of p53 protein by a mutated gene and mdm2 overexpression, are involved in fibrosarcomatous transformation in a subset of fibrohistiocytic tumours and possibly correlated with its more locally aggressive behaviour than that without p53 alterations or ordinary DFSP.[1]

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