Adult ; Cytogenetics ; Genes, p53 ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Tumor Suppressor Protein p53/genetics*

The P53 gene has the important functions including induction of apoptosis, regulation of cell cycle, repair of DNA damage. The mutation of the P53 gene exists in more than 50% of human tumors and 13% of hematological malignancies. The P53 gene abnormality is closely related with the clinical course and prognosis of leukemia. The P73 or P63 gene, the member of the P53 family not only possesses similar to P53 activity of inducing apoptosis, activating transcription, but also plays different biological effects according to protein structural diversity, and even antagonises the function of the P53 gene. Researchers found that P73 or P63 gene also has the dual characteristics of the tumor suppressor and oncogene, and shows different expression and function in different types, different stages of leukemia. In this article, P53 family (P53, P73, P63) gene structure, biological function and the relationship of the three genes with the course, prognostic outcome, treatment and other clinical features of the leukemia are reviewed.
Gene Expression Regulation, Neoplastic ; Genes, p53 ; Humans ; Leukemia ; diagnosis ; genetics ; pathology ; Tumor Suppressor Protein p53 ; genetics

Apoptosis ; Cell Proliferation ; Humans ; Neoplasms ; Tumor Suppressor Protein p53

OBJECTIVES: Mutation of p53 may play a role in manifestation of rheumatoid arthritis synovium, but several studies on p53 expression in synovial tissues of rheumatoid arthritis showed conflicting results. We investigated the amount and pattern of p53 positive cells in rheumatoid arthritis synovium, in comparison with osteoarthritis synovium, by using immunohistochemistry with two other monoclonal antibodies for p53. METHODS: Synovial tissues from 9 patients with rheumatoid arthritis and 5 patients with osteoarthritis were examined for p53 expression by immunohistochemistry with 2 monoclonal antibodies for p53, DO-1 and DO-7. Histologic features of inflammation were also scored and compared with p53 expression. RESULTS: There was no significant difference between inflammatory scores in both groups. In the synovial tissues of rheumatoid arthritis patients, p53 positive cells were detected in 3 out of 9 samples(33%) and p53 expressions were restricted to inflammatory mononuclear cells, but synovial lining cells, subsynovial fibroblast-like cells and vascular endothelial cells were p53 negative. p53 expressions in osteoarthritis synovial tissues as control were observed in 2 out of 5 samples(40%) and the amount and pattern of p53 positive cells were comparable to those seen in rheumatoid arthritis synovial tissues. There was no demonstrable correlation between the synovial tissues of both groups with respect to inflammation scores and expression of p53 protein. CONCLUSION: Our findings suggest that altered p53 expression may not play a significant role in the manifestation of rheumatoid arthritis synovium. However these data need to be strengthened by increasing the number of samples and molecular biology approaches.
Arthritis, Rheumatoid/metabolism* ; Arthritis, Rheumatoid/genetics ; Comparative Study ; Gene Expression ; Genes, p53 ; Human ; Immunohistochemistry ; Osteoarthritis/metabolism ; Osteoarthritis/genetics ; Protein p53/metabolism* ; Protein p53/genetics ; Synovial Membrane/metabolism

p53 gene mutations have been known to be highly related to the particular stage of transformation in various types of human cancers. This study was conducted to investigate the p53 mutations at the protein level by an immunohistochemical method using anti-p53 antibody, NCL-p53-DO-7. Twenty-five cancer specimens were obtained surgically from patients with squamous cell cancer of the skin at the Korea Cancer Center Hospital. The cancers were classified according to the possible etiology into two groups, burn scar originated and UV-related cancers. Overexpression of p53 protein was detected in ten (40%) out of 25 cases tested: six (40%) of 15 cases associated with burn scar and four (40%) of ten cases related to UV exposure. In all normal skin cells in specimens, p53 protein was not stained at all. The stages and histological grades were evaluated for their relationship with the overexpression of p53 protein. No significant difference was found between the overexpression of p53 protein and the stages or histological grades. These results demonstrating that 40% of skin cancers were positive for p53 overexpression suggest that the alterations of the p53 gene may play a role and the exact role of p53 gene in the development of squamous cell carcinoma of the skin will be studied.
Adult ; Aged ; Carcinoma, Squamous Cell/*chemistry ; Female ; Genes, p53 ; Human ; Male ; Middle Age ; Mutation ; Protein p53/*analysis ; Skin Neoplasms/*chemistr

Adenoviridae ; genetics ; Genes, p53 ; Genetic Therapy ; methods ; Genetic Vectors ; Humans ; Neoplasms ; therapy ; RNA Interference ; Tumor Suppressor Protein p53 ; genetics

Genes, p53 ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/genetics* ; Tumor Suppressor Protein p53/genetics*

OBJECTIVETo observe the effect of recombinant adenovirus-mediated wild-type p53 gene on the number and proteins of centrosome in K562 cells. To explore the possibility of application of wild-type p53 gene therapy in the treatment of chronic myeloid leukemia.

METHODSThe recombinant adenoviruses carrying wild-type p53 gene (Ad5 wtp53), mutant p53 gene (Ad5 mtp53) or the green fluorescent protein (GFP) gene was repeatedly amplified and co-infected into K562 cells with cation polybrene. The optimal infection titer and infection time of the recombinant adenoviruses were determined by MTT assay, p53 mRNA and protein expression were determined by RT-PCR and Western blot respectively. The centrosomal structural protein gamma-tubulin and the spindle protein alpha-tubulin were marked simultaneously by indirect immunofluorescence staining, and the expression of the centrosomal gamma-tubulin protein, the mitosis and the number of centrosome were observed under the laser confocal microscopy.

RESULTSInfection efficiency with recombinant adenoviruses was facilitated by polybrene in K562 cells, and 4 microg/ml polybrene was chosen. The optimal adenovirus infection titer was 20,000 MOI and the optimal infection time was 72 hours. p53 mRNA and P53 protein can be expressed in K562 cells by Ad5wtp53 and Ad5mtp53. Both the expression of the centrosomal gamma-tubulin protein and the number of centrosomes were decreased after Ad5wtp53 infection.

CONCLUSIONThere is sustained expression of P53 protein in K562 cells after its infection by Ad5wtp53. Wild-type P53 protein can lead to the down-regulation of the number of centrosomes and the expression of centrosomal gamma-tubulin protein in K562 cells.

Adenoviridae ; genetics ; Centrosome ; metabolism ; Genes, p53 ; genetics ; Genetic Vectors ; Humans ; K562 Cells ; Transfection ; Tubulin ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Endoscopic mucosal resection (EMR) has been standardized for the treatment of intestinal type of intramucosal gastric carcinomas, and careful histological examination of the resected specimen is important for further treatment. To evaluate the diagnostic utility of p53 expression in gastric EMR samples, using immunohistochemical staining, we examined 24 gastric carcinomas (22 intestinal types and two diffuse types) and 20 adenomas removed by EMR. Intestinal type of adenocarcinomas revealed strong p53 expression in 13 cases (59%), weak in four cases (18%), and negative in five cases (23%). Resection margins of 11 carcinomas were involved in the carcinoma cells, which showed the same p53 expression pattern with main carcinoma cells. Squeezed carcinoma cells, remaining in resection margins, were definitely identified by strong p53 expression in seven cases of which the main tumor strongly expressed p53. Microscopic in situ carcinoma could be easily detected in p53 immunostaining. Multifocal involvement and submucosal invasion of carcinomas could be demarcated easily and definitely by strong p53 expression of carcinoma cells. All adenomas showed diffuse weak p53 expression. The difference of p53 expression (p< 0.001) could be used as a differential diagnosis between adenomas and carcinomas. According to these results, we propose that for careful histological examination in hospital diagnosis, both histological evaluation and p53 immunostaining are important diagnostic parameters in EMR samples of the intestinal type of gastric carcinomas.
Adenocarcinoma/surgery ; Adenocarcinoma/pathology ; Adenoma/surgery* ; Adenoma/pathology* ; Endoscopy* ; Gastric Mucosa/metabolism ; Gastric Mucosa/chemistry ; Human ; Immunoenzyme Techniques ; Protein p53/diagnostic use* ; Protein p53/biosynthesis ; Protein p53/analysis ; Stomach Neoplasms/surgery* ; Stomach Neoplasms/pathology* ; Tumor Markers, Biological

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log- Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p= 0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma.
Adult ; Aged ; Female ; Genes, p16 ; Genes, p53 ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/*chemistry/genetics/mortality/pathology ; Protein p16/*analysis ; Protein p53/*analysis ; Sex Characteristics