Expression of the p53 protein in malignant melanomas as a prognostic indicator

Abstract

It is currently widely accepted that the tumour suppressor gene p53 is critically involved in the proliferation and differentiation of tumour cells including melanoma cells. In the present study, we examined 60 cases of primary melanoma to compare the expression of p53 protein with conventional prognostic markers for melanoma such as clinical and histological parameters. No correlation was found between the p53 protein and clinical factors except for the presence of a metastatic node and development to clinical stage II. However, the expression of p53 protein was significantly associated with tumour thickness over 1.5 mm, levels IV and V of invasion, the presence of ulceration, and high mitotic rate for 5-year survival rate. Although many questions still remain to be answered, our results and those of others for various other malignant tumours, implicate p53 in malignant transformation of pigment cells. Indeed, it could be a new marker for an unfavourable prognosis of malignant melanoma, even though the gene mutation in this highly lethal tumour has yet to be established.

Frequent mutations of the p53 gene in cutaneous melanoma of the nodular type

“…Early studies indicated an increased expression of p53 protein in almost 100% of the tumors (Stretch et al, 1991;Akslen and Mørkve, 1992;Weiss et al, 1993Weiss et al, , 1995McGregor et al, 1993), but others found a lower proportion, of 5-50% (Yamamoto et al, 1995;Lassam et al, 1993;Cristofolini et al, 1993;Flørenes et al, 1994). In the present study, marked differences in immunostaining were found using various p53 antibodies.…”

“…In cutaneous melanoma, p53 changes have been repeatedly reported. Some early studies have indicated that p53 protein expression was increased in a high proportion of primary melanomas, up to nearly 100% (Stretch et al, 1991;Akslen and Mørkve, 1992;Weiss et al, 1993Weiss et al, , 1995McGregor et al, 1993), whereas others found a lower frequency (about 5-50%) of p53 tumor positivity by immunohistochemistry (Yamamoto et al, 1995;Lassam et al, 1993;Cristofolini et al, 1993;Flørenes et al, 1994). Alterations of the p53 gene have been described in about 20-25% of metastatic cutaneous melanomas (Flørenes et al, 1994;Sparrow et al, 1995;Hartmann et al, 1996).…”

p21WAF1/CIP1 expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival

“…However, within the subgroup of patients with thick (>1.5 mm) tumours, already known to have an impaired survival, p53 index independently separated those patients into different prognostic groups. Most studies to date have shown either no correlation (Sparrow et al, 1995;Weiss et al, 1995;Talve et al, 1996) or, like our study, an inverse (Yamamoto et al, 1995;Vogt et al, 1997) correlation between the p53 expression and outcome of human cutaneous malignant melanoma.…”

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis

“…This is often in the absence of point mutations in the gene (McGregor et al, 1993;Albino et al, 1994;Sparrow et al, 1995) but is associated with tran scriptional inactivity (Houben et al, 2011). Moreover, corre lation of p53 immunoreactivity with advanced melanoma and unfavorable prognosis has been demonstrated (McGregor et al, 1993;Yamamoto et al, 1995). Small molecular weight variants of p53 have also been demonstrated in melanoma and, in some instances, are expressed at higher levels than fulllength WTp53 (AveryKiejda et al, 2008).…”

“…High levels of p53 expression in melanoma cells and tissue samples have been reported in numerous studies (Bártek et al, 1991;Stretch et al, 1991;Akslen and Mørkve, 1992;McGregor et al, 1993;Yamamoto et al, 1995;Hussein et al, 2003;Houben et al, 2011;Knopf et al, 2011). This is often in the absence of point mutations in the gene (McGregor et al, 1993;Albino et al, 1994;Sparrow et al, 1995) but is associated with tran scriptional inactivity (Houben et al, 2011).…”