The previous study detected 15/18 cases of oral squamous cell carcinoma expressing p53 positive immunostaining: 7/8 cases with p53 mutation and 8/10 cases without p53 mutation. In this study, immunohistochemical staining showed mdm2 overexpresion in 7/18 cases, combined p53/mdm2 overexpression in 6/18 cases, mdm2 overexpression in 5/8 p53-positive without mutation cases. These results indicated that p53 overexpression can be associated with p53 gene mutation, as well as mdm2 overexpression in the oral carcinogenensis
Mouth Neoplasms ; diagnosis ; Genes, p53 ; Proto-Oncogene Proteins c-mdm2

OBJECTIVES: MDM-2 is an oncoprotein that inhibits p53 tumor suppressor protein. Amplication and over- expression of its protein have been observed in human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To elucidate the role of p53 and MDM-2 protein in cervical neoplasia we investigated the expression rates of MDM-2 and p53 protein in surgically resected specimens. METHEDS: Immunohistochemical studies using anti-p53 and anti-MDM-2 protein in the paraffin embedded section of 62 cases including cervical intraepithelial neoplasm(CIN) and invasive cervical cancer were performed. RESULTS: Expression rates of p53 protein were 25% in CIN I& CINII, 20% in CINIII, and 44% in invasive carcinoma, respectively. The MDM-2 protein were 33% in CIN I & CIN II, 16% in CIN III, and 48% in invasive carcinoma, respectively. There was no evident correlation between p53 positivity and MDM-2 positivity(p>0.05). However, correlation between MDM-2 negativity and p53 negativity was statistically significant(p=0.002) CONCLUSION: These data suggest that the expression of p53 protein is presumed to be necessarily correlated with MDM-2 protein expression in cervical neoplasia.
Carcinogenesis ; Humans ; Paraffin ; Proto-Oncogene Proteins c-mdm2* ; Tumor Suppressor Protein p53 ; Uterine Cervical Neoplasms

PURPOSE: MDM-2 is an oncoprotein that inhibits p53 tumor-suppressor protein. These abnor malities have a role in tumorigenesis through inactivation of p53 function. To determine the clini copathological and prognostic value of MDM2 abnormalities in gastric adendegrees Carcinoma, MDM-2& p53 protein expression were analysed in surgically resected materials of gastric adendegrees Carcinoma. MATERIALS AND METHODS: Fifty cases which had got follow-up after surgical resection were immunohistdegrees Chemically studied with p53 and MDM-2 antibodies. We defined variable clinico pathologic factors for expression of p53 and MDM-2 protein and analysed their relationships. RESULTS: Immunohistdegrees Chemical stain revealed expression of MDM-2 protein as a 52.0% (26/50) and p53 protein 20.0% (10/50), respectively. But their expressions were not assdegrees Ciated with clinicopathological factors such as T-factor, N-factor, stage, histology and differentiation. Overall, p53-negative patients seemed to have a better prognosis regardless of MDM-2 protein status (P= 0.057). MDM-2 protein status was considered to have no play as a prognostic factor. CONCLUSION: In the gastric adendegrees Carcinoma, p53 protein expression seemed to have a inverse relationship with clinical outcomes but MDM-2 protein expression, which was observed more frequently than those of p53, seemed not to be prognostic indicator.
Antibodies ; Carcinogenesis ; Follow-Up Studies ; Humans ; Prognosis ; Proto-Oncogene Proteins c-mdm2 ; Stomach Neoplasms

BACKGROUND: In the uterine cervical carcinoma, the inactivation of p53 protein by human papillomavirus(HPV) E6 protein has been reported to play a greater role in carcinogenesis than the mutation of the p53 gene. Therefore, the mutation of the p53 gene is rare. p21 and mdm2 proteins are induced by wild-type p53 protein and are involved in the cell cycle regulatory mechanism. METHODS: Immunohistochemical staining for p53, p21 and mdm2 proteins was performed in 26 HPV-positive and 13 HPV-negative invasive cervical carcinomas together with 5 non-neoplastic cervical tissues. RESULTS: The frequencies of the expression of p53, p21 and mdm2 proteins were 82.1%, 84.6% and 66.7%, respectively. The expression of p53 protein was less frequently demonstrated in HPV-positive cases than HPV-negative cases, which was statistically a negative correlation(p=0.018). The expression of p53 and p21 proteins was statistically significant(p=0.000). CONCLUSIONS: p53, p21 and mdm2 proteins were highly expressed in both HPV-positive and HPV-negative cervical carcinomas. Significantly higher expression of p53 protain in HPV-negative cases necessitate a further study for investigating the role of p53 protein accumulation in carcinogenesis of HPV-negative cervical carcinomas. The relationship between the expression of p53 protein and p21/mdm2 proteins may indicate that p21 and mdm2 proteins also have a role in carcinogenesis, where p53 protein plays a fundamental role.
Carcinogenesis ; Cell Cycle ; Genes, p53 ; Humans* ; Proto-Oncogene Proteins c-mdm2* ; Uterine Cervical Neoplasms

PURPOSE: To evaluate the relationships between mutations of the p53 and MDM-2 proteins in human primary chondrosarcoma and in secondary chondrosarcoma from osteochondromatosis. MATERIALS AND METHODS: From January, 1984 to April, 2000, 33 cases were grouped into three categories: Group I, osteochondromatosis (18 cases), group II, secondary chondrosarcoma (6 cases), group III, primary chondrosarcoma (9 cases). We analysed the expressions of the p53 and MDM-2 proteins. All specimens were embedded in paraffin and stained using the Streptavidin-Biotin peroxidase method with anti-p53 antibody, and DO7 anti-MDM-2 antibody IF2 as monoclonal antibody. RESULTS: The expressions of the p53 and MDM-2 proteins, the pathologic grade of each group, and clinical outcomes were compared and analysed. The expressions of the p53 and MDM-2 proteins in each group were significantly different (p<0.05). However, MDM-2 protein expression was similar between group II and III. Both p53 and MDM-2 protein were expressed most frequently in group III and this was significant. There was an increased manifestation of the p53 and MDM-2 protein in the higher pathologic grade. The 5-year survival rate of patients with a malignant tumor was about 70%. In expired patients, the histologic grade was grade III, and both proteins were expressed, which enabled a relationship to be established between p53 and MDM-2 protein expression and a poorer prognosis. CONCLUSION: In osteochondromatosis, the coexpression of the p53 and MDM-2 proteins was not observed, but isolated p53 or MDM-2 expression was observed in some cases. According to this study, it is helpful as a basic study for early detection of malignant translation of osteochondromatosis. In conclusion, we suggest that the expressions of the p53 and MDM-2 proteins are useful indicators of prognosis.
Chondrosarcoma* ; Humans ; Osteochondromatosis* ; Paraffin ; Peroxidase ; Prognosis ; Proto-Oncogene Proteins c-mdm2 ; Survival Rate

BACKGROUND: The human homologue of mouse double minute 2(mdm-2) gene codes for a cellular protein that forms a complex with the mutant and wild type p53 protein and modulates its trans-activation activity. Overexpression of the mdm-2 protein is associated with the tumorigenic potential of mdm-2 gene and overcomes the growth suppressive activity of p53. OBJECTIVE & METHODS: In order to investigate the pattern of the mdm-2 and p53 expression in malignant skin tumors, we performed an immunohistochemical analysis using NCL-MDM-2p polyclonal antibody and DO7 monoclonal antibody, respectively, in 10 squamous cell carcinomas (SCCs), 8 basal cell carcinomas(BCCs), 5 malignant melanomas(MMs), and 6 fibrosarcomas (FSs). RESULTS: The expression of mdm-2 protein was detected in 40% of SCCs, 25% of BCCs, 40% of MMs and 33% of FSs, whereas 40% of SCCs, 25% of BCCs, 20% of MMs, and 17% of FSs showed p53 positivity. One case of SCCs and one case of BCCs showed immunoreactivity with both anti-mdm-2 and anti-p53 antibodies. Within the limitations of this small sample size, there was no relationship between the expression of mdm-2 and p53 protein, as overexpression of these two genes was not mutually exclusive. CONCLUSION: These findings suggest that interaction between the mdm-2 and p53 genes and products in these malignant tumors appears to be heterogenous and more complex than previously realized. Further studies on molecular basis are required to characterize the mechanism of mdm-2 overexpression and its relation to p53.
Animals ; Antibodies ; Carcinoma, Squamous Cell ; Fibrosarcoma ; Genes, p53 ; Humans ; Melanoma ; Mice ; Proto-Oncogene Proteins c-mdm2 ; Sample Size ; Skin*

BACKGROUND: MDM2 (mouse double minute 2), the product of an oncogene is a key regulator of p53. It can repress transcription of p53 and eliminate it through proteolytic degradation. On the other hand, p53 binds specifically to the MDM2 and stimulates its transcription. Thus the two molecules are linked to each other through an autoregulatory feedback loop. OBJECTIVE: To evaluate the expression patterns of p53 and MDM2 in several epithelial tumors and assess their correlations. METHODS: We investigated the expression of p53 and MDM2 protein by an immunohistochemical method on formalin-fixed, paraffin-embedded tissue specimens of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease, and actinic keratosis (AK). RESULTS: The expression of p53 was increased in 83.3% (15/18) of BCC, 87.5% (14/16) of SCC, 75.0% (12/16) of Bowen's disease, and 57% (8/14) of AK. The expression of MDM2 was increased in 50.0% (9/18) of BCC, 25.0% (4/16) of SCC, 68.8% (11/16) of Bowen's disease, and 14.3% (2/14) of AK. The expression level of p53 had a significant positive correlation with the expression level of MDM2 in actinic keratosis (p=0.022). There was no correlation between the expression level of these two markers in others (p>0.05). CONCLUSION: This data suggests that p53 and MDM2 may be associated with pathogenesis of skin epithelial tumors with complex pathways. p53 (+)/MDM2 (+) phenotype expression may have an important pathogenetic role in Bowen's disease. p53 (+)/MDM2 (-) type expression may have an important pathogenetic role in BCC, SCC, and AK. In particular, in AK p53 (+)/MDM2 (-) phenotype expression may have a major pathogenetic role. The mechanism of how they interact to promote tumorigenesis and the prognostic values in skin epithelial tumors remains to be elucidated though.
Bowen's Disease ; Carcinogenesis ; Carcinoma, Basal Cell ; Carcinoma, Squamous Cell ; Hand ; Keratosis, Actinic ; Oncogenes ; Phenotype ; Proto-Oncogene Proteins c-mdm2 ; Skin*

Apoptosis ; drug effects ; Hep G2 Cells ; Hepatoblastoma ; metabolism ; Humans ; Oligonucleotides, Antisense ; pharmacology ; Proto-Oncogene Proteins c-mdm2 ; genetics

BACKGROUNDP53 is one of the most studied tumor suppressors in the cancer research, and over 50% of human tumors carry P53 mutations. MDM-2 is amplified and/or overexpressed in a variety of human tumors of diverse tissue origin. The aim of this study was to examine the expression of P53 protein and MDM-2 protein in gliomas, and to investigate the relationship between the expression of the two proteins and the histopathological grades of glioma. The relationship between MDM-2 protein expression and P53 protein expression was also analyzed.

METHODSThe expression of P53 protein and MDM-2 protein was immunohistochemically detected using monoclonal antibodies in 242 paraffin embedded tissues, including 30 normal brain tissues from patients with craniocerebral injury and 212 tissues from patients with primary glioma (grade I - II group: 5 cases of grade I, 119 cases of grade II; and grade III--IV group: 53 cases of grade III, and 35 cases of grade IV).

RESULTSThe P53 positive rate was significantly higher in the glioma groups than in the control group (P < 0.0001). The P53 positive rate was significantly higher in glioma tissues of grade III - IV than in glioma tissues of grade I - II group (P = 0.001). The MDM-2 positive rate was significantly higher in glioma groups than in the control group (P < 0.0001). There was no significant difference in the MDM-2 positive rate between the two glioma groups (P = 0.936). The expression of P53 protein was not related to expression of MDM-2 protein (P = 0.069)

CONCLUSIONSOverexpression of P53 protein might be related to the occurrence and progression of glioma. Overexpression of MDM-2 protein may play an important role in glioma tumorigenesis, but may not be involved in glioma progression. The overexpression of MDM-2 protein was an early event in malignant transformation of glioma. MDM-2 may be a key player in glioma in its own right.

Glioma ; metabolism ; pathology ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Proto-Oncogene Proteins c-mdm2 ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.
Biomarkers, Tumor/genetics* ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Liposarcoma/genetics* ; Proto-Oncogene Proteins c-mdm2/genetics* ; RNA