MDM-2 Protein

Sources/Clones
Accurate (19E3), Dako (SMP14), Novocastra (1B10, polyclonal), and Oncogene (1F2).

Fixation/Preparation
Several of the antibodies are immunoreactive in fixed paraffin-embedded tissue sections and also fresh tissue and cell preparations.

Background
The MDM-2 protein encodes for a nuclear phosphoprotein that binds p53 and inhibits its ability to activate transcription by concealing the p53 activation domain. It has been suggested that MDM-2 overexpression might represent an alternative mechanism by which p53-mediated pathways are inactivated in human tumors, thus having a possible role in oncogenesis. MDM-2 overexpression as a result of gene amplification and/or increased mRNA expression can be detected by immunohistochemical analysis.

Applications
The ability to stain for MDM-2 protein in fixed tissue sections has stimulated a great deal of interest in its expression in various neoplasms. The correlation of MDM-2 protein levels with p53 may provide insights into oncogenesis and has the potential of providing prognostic information. Several studies have included the detection of p21/waf1 protein together with MDM-2 as both these oncoproteins are downstream effectors of p53, p21 playing a major role in negatively regulating cell cycle progression, while MDM-2 inhibits the effects of p53.
Current results of immunohistochemical analyses of MDM-2 and p53 protein are far from conclusive, although many support an inverse correlation between the two oncoproteins. Such studies have included uterine sarcoma (Seki et al, 1997), breast carcinoma (Jiang et al, 1997), thymoma (Stefanaki et al, 1997), osteogenic sarcoma (Lonardo et al, 1997), glioblastoma (Biernat et al, 1997), lung carcinoma (Higashiyama et al, 1997), oral carcinoma (Matsumura et al, 1996), malignant melanoma (Gelsleichter et al, 1995), thyroid carcinoma (Jennings et al, 1995) and rhabdomyosarcoma (Keletti et al, 1996).

Comments
Immunostaining for MDM-2 has also been successfully conducted on cytological preparations (Dowell et al, 1996).

References
•Biernat W, Kleihaues P, Yonekawa Y, Ohgaki H 1997. Amplification and overexpression of MDM2 in primary (de novo) glioblastomas. Journal of Neuropathology and Experimental Neurology 56: 180-185.

•Dowell SP, McGoogan E, Picksley SM et al 1996. Expression of p21waf1/Cip1, MDM2 and p53 in vivo: analysis of cytological preparations. Cytopathology 7: 340-351.

•Gelsleichter L, Gown AM, Zarbo RJ et al 1995. P53 and mdm-2 expression in malignant melanoma: an immunocytochemical study of expression of p53, mdm-2, and markers of cell proliferation in primary versus metastatic tumors. Modern Pathology 8: 530-535.

•Higashiyama M, Doi O, Kodama K et al 1997. MDM2 gene amplification and expression in non-small cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. British Journal of Cancer 75: 1302-1308. cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. British Journal of Cancer 75: 1302-1308.

•Jennings T, Bratslavsky G, Gerasimov G et al 1995. Nuclear accumulation of MDM2 protein in well-differentiated papillary thyroid carcinoma. Experimental and Molecular Pathology 62: 199-206.

•Jiang M, Shao ZM, Wu J et al 1997. P21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis. International Journal of Cancer 74: 529-534.

•Keletti J, Quezado MM, Abaza MM et al 1996. The MDM2 oncoprotein is overexpressed in rhabdomyosarcoma cell lines and stabilizes wild-type p53 protein. American Journal of Pathology 149: 143-151.

•Lonardo F, Ueda T, Huvos AG et al 1997. P53 and MDM2 alterations in osteosarcomas: correlation with clinicopathologic features and proliferative rate. Cancer 79: 1541-1547.

•Matsumura T, Yoshihama Y, Kimura T et al 1996. P53 and MDM2 expression in oral squamous cell carcinoma. Oncology 53: 308-312.

•Seki A, Kodaman J, Miyagi Y et al 1997. Amplification of the mdm-2 gene and p53 abnormalities in uterine sarcomas. International Journal of Cancer 73: 33-37.

•Stefanaki K, Rontogianni D, Kouvidou CH et al 1997. Expression of p53, mdm2, p21/waf1 and bcl-2 proteins in thymomas. Histopathology 30: 549-555.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.