p53

p53 is a tumour suppressor gene located on the short arm of chromosome 17. The gene product is a 53-kDa nuclear phosphoprotein involved in transcription regulation and cell growth. Mutations of p53 are the most commonly detected genetic abnormality in human neoplasia10. Mutations induce a conformal change in the protein, rendering it stablised. For this reason, nuclear overexpression of p53 by immunohistochemistry correlates with p53 mutations. However, in some cases, p53 positivity occurs without detectable mutations12,13. Lower levels of immunoreactivity may result from stabilisaton of wild type p53 by other mechanisms. Conversely, mutations may occur without detectable levels of p53 protein13. In one study of non-Hodgkin lymphoma, point mutations of p53 were only observed in cases that were negative for p21WAF1 18.

Immunostaining for p53 requires appropriate antigen retrieval21: immunoreactivity is lost in slides stored at room temperature but is restored by microwave heating22. Different antibodies appear to recognise different epitopes. A range of antibodies (PAb 1801, DO1, DO7, BP53.12 and 421) have been shown to recognise nuclear p53 but only BP53.12 and 421 recognise cytoplasmic p5319. PAb 1801 and DO7 have been recommended for routine use20.

Immunohistochemical expression

lung carcinoma: 33% of cases1, 6/19 bronchioloalveolar carcinomas2

	squamous carcinoma	14/257
	adenocarcinoma	28/467
	adenosquamous carcinoma	1/37
	large cell carcinoma	7/117

malignant phyllodes tumours are positive, while benign phyllodes tumours and fibroadenomas are negative.3
gastric carcinoma: 23/805
overexpressed in 24/28 cholangiocarcinomas3
ovarian caner, particularly of serous type. Mutations of p53 have been reported in 8% of low grade and 51% of high grade serous carcinomas of the ovary8.
Cervical high-grade intraepithelial neoplasia with low expression of both p53 and retinoblastoma protein (p53 <15% of nuclei, pRb < 40% of nuclei) is highly likely to persist, in contrast to those cases where one of these cell regulators is strongly expressed9.

Diagnostic utility

concurrent p53 and c-erbB-2 overexpression are indicators of poor prognosis in node-negative breast carcinoma6.
p53 expression is associated with a worse survival in stage I non-small cell carcinoma of lung7.
Overexpression of p53 correlates with recurrence and poor survival in transitonal cell carcinoma of the bladder23.
p53 positive follicular lymphomas may be at risk for progression and in this subset aggressive therapy may be warranted11.
Mutations of p53 may be one mechanism involved in the development of variant forms of mantle cell lymphoma and p53 mutations in mantle cell lymphoma may predict a poor prognosis14,15,16.
p53 expression has been found to be a marker of failure to respond to chemotherapy and of poor prognosis in high grade B-cell lymphomas10,17.
Differentiation of reactive mesothelial cells (negative) from malignant cells (positive) in effusions.
Differentiation of type I and type II endometrial carcinoma