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 neoplasia. Mutations induce a conformal change in the protein, rendering it stablised. For this reason, nuclear overexpression of p53 by immunohistochemistry correlates with p53 mutations. Lower levels of immunoreactivity may result from stabilisaton of wild type p53 by other mechanisms.

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.

• Differentiation of reactive mesothelial cells (negative) from malignant cells (positive) in effusions.

• Differentiation of type I and type II endometrial carcinoma

References

¹ Greenblatt, M. S., Bennett, W. P., Hollstein, M., Harris, C. C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis Cancer Res 1994;54:4855-4878.

² McDonald, J. W., Pilgram, T. K. Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma Histopathology 1999;34:439-446.3Histopathology 1999;34:439-446.

³ Millar, E. K., eretov, J., Marr, P., Sarris, M., Clarke, R. A., Kearsley, J. H., Lee, C. S. Malignant phyllodes tumours of the breast display increased stromal p53 protein expression. Histopathology 1999;34:491-6.

⁴ Arora, D. S., Ramsdale, J., Lodge, J. P., Wyatt, J. I. p53 but not bcl-2 is expressed by most cholangiocarcinomas: a study of 28 cases Histopathology 1999;34:497-501.

⁵ Kume, T., Oshima, K., Shinohara, T., Takeo, H., Yamashita, Y., Shirakusa, T., Kikuchi, M. Low rate of apoptosis and overexpression of bcl-2 in Epstein-Barr virus- associated gastric carcinoma Histopathology 1999;34:502-509.

⁶ Rudolph, P., Alm, P., Olsson, H., Heidebrecht, H. J., Ferno, M., Baldetorp, B., Parwaresch, R. Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer. Human Pathol 2001;32:311-319.

⁷ Han, H., Landreneau, R. J., Santucci, T. S., Tung, M. Y., Macherey, R. S., Shackney, S. E., Sturgis, C. D., Raab., S. S., Silverman, J. F. Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2 in stage I non-small-cell lung cancer. Human Pathol 2002;3:105-110.

⁸ Singer G, Stohr R, Cope L, et al. Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am J Surg Pathol 2005; 29:218-24

⁹ Baak JP, Kruse AJ, Garland SM, et al. Combined p53 and retinoblastoma protein detection identifies persistent and regressive cervical high-grade squamous intraepithelial lesions. Am J Surg Pathol 2005; 29:1062-6

This page last revised 19.11.2005.

©SMUHT/PW Bishop