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

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

BACKGROUND: Gastric carcinomas (GCs) have recently been reclassified according to the mucin phenotypes. We aimed to characterize the relationship between the mucin phenotypes and the genetic alterations or the clinicopathologic parameters of GCs. METHODS: Immunohistochemistry was performed for MUC1, MUC5AC, MUC6, MUC2, CD10, p53, hMLH1, CerbB2 and E-cadherin in 150 GCs. The mucin phenotypes of the GCs were classified as 4 phenotypes: gastric, intestinal, mixed and unclassified. RESULTS: MUC1, MUC5AC, MUC6, MUC2 and CD10 were expressed in 63.3%, 42.7%, 14.0%, 24.7% and 14.0% of the GCs, respectively. The mucin phenotypes of the GCs corresponded to the gastric type in 31.3%, the intestinal type in 20.0%, the mixed type in 15.3% and the unclassified type in 33.3%. The incidence of a p53 overexpression was higher in the gastric or mixed phenotype than in the intestinal or unclassified phenotype. MUC5AC expression, p53 overexpression and the gastric or mixed phenotype were associated with poor patient survival by multivariate analysis. CONCLUSION: This study suggests the gastric or mixed mucin phenotype may more likely go through the p53 pathway in carcinogenesis and the mucin phenotype may be considered as a prognostic indicator.
Cadherins ; Carcinogenesis ; Humans ; Immunohistochemistry ; Incidence ; Mucins* ; Multivariate Analysis ; Phenotype* ; Stomach ; Tumor Suppressor Protein p53

OBJECTIVE: To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R). METHODS: Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared. RESULTS: Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, <0.01, <0.01, 0.046, respectively). The IPSS-R scores of MDS patients with mutations were significantly higher than the wild types (P<0.01). The IPSS-R scores of the TP53 mutation groups were 7.82±1.83, which was significantly higher than the control group (3.77±1.66, P<0.01). No difference was found between the IPSS-R between patients carrying TET2, ASXL1, RUNX1, and SF3B1 mutations or the wild types (P>0.05). CONCLUSION Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.
DNA Mutational Analysis ; Humans ; Incidence ; Mutation ; Myelodysplastic Syndromes ; genetics ; Prognosis ; Tumor Suppressor Protein p53 ; genetics

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

OBJECTIVETo study the prevalence of P53 protein expression and p53 gene mutation in laryngeal carcinoma.

METHODSUsing immunohistochemistry P53 expression was detected in 31 patients with laryngeal carcinoma. In 11 P53 negative patients,microdissection-PCR-HA technique was used to determine mutation in p53 exon 5, 6, 7, 8.

RESULTSAmong the 31 patients tested with immunostaining, the overall average positive rate was 64.5%. Positive rates for T3 and T4 tumors were 86.7% vs 43.8% in T1 and T2 tumors.The positive rate was 91.7% in those with cervical node metastasis compared with 47.4% in those without lymph node metastasis. The positive P53 immunostaining was more frequently found in poor differentiated carcinoma (87.5%) and moderate-differentiated carcinoma (66.7%),than in well differentiated carcinoma (45.5%). The abnormal exon 5 or 7 of p53 gene were detected in 2 out of 11 cases, in which P53 was negative.

CONCLUSIONP53 gene mutation is related with TNM grading and cervical lymph node metastasis in laryngeal carcinoma. P53 mutation tents to be correlated to pathologic grading.

Adult ; Aged ; Female ; Genes, p53 ; Heteroduplex Analysis ; Humans ; Immunohistochemistry ; Laryngeal Neoplasms ; chemistry ; genetics ; Male ; Middle Aged ; Mutation ; Tumor Suppressor Protein p53 ; analysis

OBJECTIVESTo explorer the change of several signal pathway and their signal after liver transplantation.

METHODSClassified 34 punctured donor liver samples and 10 normal liver samples as A (no rejection) groups, B (mild/moderate acute rejection) groups, C (serious acute rejection) groups, D (chronic rejection/fibrosis) groups and E (control) groups, MAPK, Ras and p53 were performed immunohistochemistry analysis and image analysis. MAPK and Ras were performed in situ hybridizition. Then image analysis was performed.

RESULTSThe protein expression of MAPK, Ras, increase by turns of A, B and C groups (1.42+/-0.28, 3.88+/-0.87, 6.68+/-0.57 in MAPK; 1.27+/-0.12, 2.80+/-0.30, 3.93+/-0.20 in Ras; corresponding), and decrease by turns of D and E groups (1.49+/-0.37, 0.88+/-0.20 in MAPK; 1.47+/-0.21, 1.01+/-0.12 in Ras; corresponding, F=178.39 in MAPK and 320.59 in Ras, groups B, C vs groups A, D, E, P<0.001 in MAPK and Ras), The protein expression of p53 is higher in treated groups (The results of groups A to E are 2.09+/-0.13, 2.39+/-0.11, 2.03+/-0.19, 2.26+/-0.18 and 0.35+/-0.08, corresponding, F=360.08, groups E vs groups A, B, C, D, P<0.001). Expression of MAPK, Ras mRNA is as same as that of protein.

CONCLUSIONThe MAPKs pathway has role in rejection response after liver transplantation. And it seemed that the MAPKs and p53 are one regulation mechanism for protecting the hepatocyte from damage after liver transplantation.

Humans ; Immunohistochemistry ; In Situ Hybridization ; Liver Transplantation ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases ; analysis ; Signal Transduction ; physiology ; Tumor Suppressor Protein p53 ; analysis ; ras Proteins ; analysis

Authors performed an immunohistochemical analysis using monoclonal antibody to p53 protein on 15 cases of benign and malignant phyllodes tumor of the breast along with a review of other conventional clinicopathological parameters to investigate the meaning of p53 expression. The cases were composed of 8 benign and 7 malignant lesions. The pattern of p53 expression showed a statistically significant difference between these benign and malignant lesions (p<0.005). None of the benign cases expressed p53 whereas 6 out of 7 malignant cases did. Among malignant phyllodes tumors, the pattern of expression was diffuse and strong in two cases while granular and relatively weak in the remaining 4 cases. p53 expression seemed to be a unique feature of malignant phyllodes tumors, thereby, one of the most significant parameters for the differentiation of benign and malignant phyllodes tumors of the breast.
Adult ; Breast Neoplasms/*chemistry/pathology ; Female ; Genes, p53 ; Humans ; Immunohistochemistry ; Middle Aged ; Phyllodes Tumor/*chemistry/pathology ; Tumor Suppressor Protein p53/*analysis

According to the current concept of carcinogenesis, the alterations of p53 tumor suppressor gene have been the most frequently detected in both human cancer cell lines and cancer tissues freshly isolated. This study was conducted to investigate the p53 gene alteration in malignant melanoma. Nineteen tumor tissues were obtained from 19 patients with malignant melanoma and examined for the expression of p53 protein by immunohistochemical staining with mouse monoclonal anti-p53 antibody, NCL-p53-DO-7. Twelve out of 19 cases (63%) showed positive reactions for p53 protein: 26, 21 and 16% of which had low, intermediate and high reactivity, respectively. p53 alteration more frequently expressed in female (10/12) than male patients (2/7) with malignant melanoma (p<0.05). The incidence of expression of p53 protein was compared according to the stages and the sites of tissue obtained. The positive rate for p53 protein was not significantly different between the stages. The positive rates for p53 protein were five out of five (100%), one out of two (50%) and six out of twelve (50%) in tissues obtained from the metastatic, lymph node, and primary sites, respectively. The difference in the positive rates, however, is not statistically significant. These results suggest that p53 gene is a frequent target for mutation in the development of malignant melanoma.
Adult ; Aged ; Aged, 80 and over ; Female ; Genes, p53 ; Human ; Immunohistochemistry ; Male ; Melanoma/genetics/*metabolism ; Middle Age ; Protein p53/*analysis ; Sex Factors ; Support, Non-U.S. Gov't

OBJECTIVETo detect gene mutations of p53 gene (exon 4-6) in fibroblasts.

METHODSSamples of keloids were taken from 15 patients. The mutations of p53 gene were detected using polymerase chain reaction, the single-strand conformational polymorphism(SSCP) analysis and DNA sequencing.

RESULTSGene mutations in p53 gene exon 4, 5, and 6 were identified in all the patients with keloids.

CONCLUSIONGene mutations resulted in keloid p53 protein losing its functions of suppressing cell processes and conducting apoptosis.

Apoptosis ; Base Sequence ; Exons ; genetics ; Fibroblasts ; Genes, p53 ; Humans ; Keloid ; genetics ; Mutation ; Polymerase Chain Reaction ; methods ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA ; Tumor Suppressor Protein p53 ; genetics