DERMATOFIBROSARCOMA PROTUBERANS WITH FIBROSARCOMATOUS AREAS - MOLECULAR ABNORMALITIES OF THE P53 PATHWAY IN FIBROSARCOMATOUS TRANSFORMATIONOF DERMATOFIBROSARCOMA PROTUBERANS

Fibrosarcomatous (FS) change in a rare, but well-known phenomenon enco untered in dermatofibrosarcoma protuberans (DFSP), and an increased ch ance in an adverse outcome has been suggested in patients with DFSP ha ving FS areas (DFSP-FS). As altered p53 pathway has been suggested as having a potential role in tumour progression, we analysed the p53 gen e and p53 protein together with the p53-related protein mdm2 and p21(W afl) in 5 cases of DFSP-FS and 13 of DFSP to ascertain whether the p53 pathway correlates to the fibrosarcomatous transformation of DFSP. Th ree of the five DFSP-FSs overexpressed p53 protein immunohistochemical ly, and one of them had a ''missense'' mutation of the p53 gene withou t immunohistochemical overexpression of mdm2 or p21(Wafl). The other t wo DFSP-FSs with p53 overexpression demonstrated increased labelling i ndices of both mdm2 and p21(Wafl). The three DFSP-FS patients with ove rexpression of p53 protein had frequent local recurrences, ranging fro m 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 overe xpressions of p53, mdm2 and p21Wafl, except for one DFSP having a ''si lent'' mutation of the p53 gene. Three DFSPs had local recurrences onc e or twice with longer intervals to recurrence (mean 10.3 years). Alth ough 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 fibrosarco matous transformation in a subset of fibrohistiocytic tumours and poss ibly correlated with its more locally aggressive behaviour than that w ithout p53 alterations or ordinary DFSP.