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The p53 protein detected by immunohistochemical staining is not always mutant
Author(s) -
Barnes Diana M.,
Fisher Charlotte J.,
Rasbridge Simon A.,
MacGeoch Catriona,
Lane David P.
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240531147
Subject(s) - staining , immunohistochemistry , biology , mutation , mutant , pathology , cancer research , negative stain , carcinoma , gene , microbiology and biotechnology , genetics , medicine , immunology , electron microscope , physics , optics
Abstract In human mammary carcinoma, positive immunohistochemical staining for p53 protein is not always indicative of mutation in the p53 gene. Although positive staining is seen in excess of 50% of tumours, mutations have been found in only some 20% of cases. In this presentation, positive p53 staining in mammary carcinomas will be related to the presence and absence of mutation and other possible underlying mechanisms. In some positively stained tumours a mutation has been found. In others, no mutation has been demonstrated and apart from possible stabilisation by a protein such as MDM2, there are alternative underlying mechanisms for this discrepancy. Wild type p53 is elevated in response to DNA damage. This effect can be seen in patients given pre‐operative chemotherapy and in cell lines irradiated with UV light and with x‐rays. Strong positive staining in scattered nuclei has been found in cell lines with activated ras and myc genes. We postulate that this may also be the reason for similar patterns observed in human tumours. Comparable mechanisms may be active in inherited cancers. Although positive p53 staining in some Li‐Fraumeni syndrome patients is associated with mutation, in other Li‐Fraumeni‐like families, no mutation has been found despite positive staining in tumour and normal tissues. Whatever the mechanism underlying the stabilisation of the protein, increased expression of p53 protein in the majority of tumour cells appears to be associated with poor prognosis in breast carcinoma.