MDM2 Immunohistochemistry Research Articles

The utility of MDM2 and CDK4 immunohistochemistry in needle biopsy interpretation of lipomatous tumours: a study of 21 Tru‐Cut biopsy cases

HistopathologyVolume 52, Issue 7 p. 892-895 The utility of MDM2 and CDK4 immunohistochemistry in needle biopsy interpretation of lipomatous tumours: a study of 21 Tru-Cut biopsy cases F Brimo, F Brimo Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorD Dion, D Dion Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorH Huwait, H Huwait Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorR Turcotte, R Turcotte Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorA Nahal, A Nahal Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this author F Brimo, F Brimo Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorD Dion, D Dion Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorH Huwait, H Huwait Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorR Turcotte, R Turcotte Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this authorA Nahal, A Nahal Departments of Pathology and Orthopedic Surgery, McGill University Health Center, Montreal, Quebec, CanadaSearch for more papers by this author First published: 25 April 2008 https://doi.org/10.1111/j.1365-2559.2008.03030.xCitations: 11Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume52, Issue7June 2008Pages 892-895 RelatedInformation

Discriminating functional and non-functional p53 in human tumours by p53 and MDM2 immunohistochemistry

Mutation and/or loss of the TP53 tumour suppressor gene is the single most common genetic abnormality in human cancer. The majority of TP53 mutations lead to stabilization of the protein, so that immunohistochemical staining for p53 can suggest mutation status in many cases. However, various false-positive and false-negative situations mean that simple immunostaining for p53 is not informative in a substantial number of tumours. In the present study, a series of 119 human cancers were immunostained using a highly sensitive technique that detects the low levels of wild-type protein expressed in normal cells, such that homozygous gene deletion or non-sense TP53 mutation can be identified by an absence of staining. TP53 gene status was also assessed using FASAY as a genetic/functional screen and in selected cases by direct sequencing. A quantitative scoring system was employed to assess p53 levels, and p53 post-translational modification was evaluated using antibodies that detect specific phosphorylation sites. Phosphorylated p53 correlated with total p53 levels and did not improve the prediction of TP53 mutation status. The transcriptional activity of TP53 was determined by staining for two downstream target genes, p21(WAF1) and MDM2, and statistical correlations between MDM2/p21(WAF1) and p53 were found in tumours with wild-type, but not mutant TP53. Measurement of staining for p53 and MDM2 accurately identifies the TP53 status of tumours. This simple and cost-effective method, applicable to automated staining and quantitation methods, improves the identification of TP53 status over standard methods for p53 immunostaining and provides information about tumour p53 phenotype that is complementary to genotyping data.

Relative quantitation of p53 and MDM2 gene expression in leiomyosarcoma; real-time semi-quantitative reverse transcription-polymerase chain reaction

To investigate the etiology of leiomyosarcoma, we examined abnormalities of p53 and its regulation in 13 cases of leiomyosarcoma using fresh tumor specimens. We estimated p53 and MDM2 mRNA level and MDM2 gene amplification using a real-time semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) based on the TaqMan fluorescence method. We also used immunohistochemistry (IHC) for p53 and MDM2 protein overexpression, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing to detect p53 mutation. Eight of the 13 cases (62%) showed an overexpression of p53 protein on IHC and eight of 13 cases (62%) had p53 gene point mutations. Five of the 13 cases (38%) showed positive staining for MDM2 protein and only one case (7.7%) demonstrated MDM2 gene amplification. The relative p53 mRNA level of the tumors compared with normal tissue ranged from 1.14 to 12.19 arbitrary units (AU), and the MDM2 mRNA level ranged from 1.06 to 17.17 AU. The mRNA level in the p53-positive cases was higher than in the negative cases (positive: 7.70 AU on average; negative: 3.38 AU on average; P=0.0344). However, there was no significant correlation between the MDM2 mRNA level and other factors, such as p53 IHC, p53 mutation status, p53 mRNA level and MDM2 IHC. Our results indicate that p53 abnormalities are major events and that an increasing level of p53 mRNA is associated with an overexpression of p53 protein in leiomyosarcoma and they may play an important role in the tumorigenesis in this tumor.