Immunohistologic Evaluation of Putatively Mutant p53 Protein in Cutaneous Melanocytic Neoplasms

Abstract

Mutations in the p53 tumor suppressor gene, located at chromosomal locus 17pI3, are the most commonly seen genetic alterations found in human malignancies. Their role in the pathogenesis of malignant melanoma is thought to be limited, although variable results have been reported in reference to immunoreactivity for putatively mutant p53 protein (mp53) in melanocytic lesions in general. In that light, the authors undertook an immunohistologic evaluation of 256 well-characterized tumors in that category, including common nevi (CN; n=73); Spitz nevi (SN; n=40); nodular melanomas (NMMs; n=32), superficial spreading melanomas (SMMs; n=65); lentigo maligna melanomas (LMMs; n=23); and melanomas arising in preexisting nevi (MANs; n=23). One hundred cells were counted manually in randomly selected high-power microscopic fields, in regard to nuclear labeling for mp53. Results were recorded semiquantitatively, as negative, positive (1-4% of tumor cells); and positive (>5% of tumor cells). No examples of CN or SN demonstrated any immunoreactivity whatever for mp53, whereas 105 of 143 melanomas (73%) did so. However, an mp53 index of >50% was seen in only 29% of the latter lesions. NMMs were most often mp53-positive and showed the highest numerical level of nuclear labeling, followed in respective order by SMMs, and LMMs/MANs. These results suggest that negative mp53-immunostaining cannot be equated with the diagnostic interpretation of a benign melanocytic neoplasm, because 27% of melanomas also failed to label for that determinant. However, the presence of mp53-immunolabeling in a melanocytic proliferation-even if at low levels-should conversely prompt careful consideration of melanoma as the favored diagnosis in the confined setting of morphologically difficult cases, inasmuch as no example of CN or SN in this series had that characteristic.