1.Genetic Expression Pattern of Gastric Carcinomas According to Cellular Mucin Phenotypes.
Won Ae LEE ; In Soo SUH ; Ying Hua LI ; Ji Hyun EUM ; Wan Sik YU ; Han Ik BAE
Korean Journal of Pathology 2007;41(5):307-315
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
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Carcinogenesis
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Humans
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Immunohistochemistry
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Incidence
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Mucins*
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Multivariate Analysis
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Phenotype*
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Stomach
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Tumor Suppressor Protein p53
2.Analysis of mutations of 14 genes among 87 patients with myelodysplastic syndrome.
Xuyan ZHOU ; He JIN ; Qitian MU ; Lixia SHENG ; Binbin LAI ; Huiling ZHU ; Guifang OUYANG
Chinese Journal of Medical Genetics 2019;36(10):953-956
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
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Humans
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Incidence
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Mutation
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Myelodysplastic Syndromes
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genetics
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Prognosis
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Tumor Suppressor Protein p53
;
genetics
3.Patterns of p53 expression in phyllodes tumors of the breast: an immunohistochemical study.
Journal of Korean Medical Science 1993;8(5):325-328
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
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Breast Neoplasms/*chemistry/pathology
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Female
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Genes, p53
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Humans
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Immunohistochemistry
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Middle Aged
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Phyllodes Tumor/*chemistry/pathology
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Tumor Suppressor Protein p53/*analysis
4.Alteration of P53 protein expression and p53 gene in laryngeal carcinoma.
Journal of Zhejiang University. Medical sciences 2003;32(3):237-240
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
5.The Role of TWIST in Ovarian Epithelial Cancers.
Kyungbin KIM ; Eun Young PARK ; Man Soo YOON ; Dong Soo SUH ; Ki Hyung KIM ; Jeong Hee LEE ; Dong Hoon SHIN ; Jee Yeon KIM ; Mee Young SOL ; Kyung Un CHOI
Korean Journal of Pathology 2014;48(4):283-291
BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway. METHODS: We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1alpha (HIF1alpha), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters. RESULTS: The expression of TWIST, E-cadherin, HIF1alpha, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1alpha expression and reduced E-cadherin expression. The altered HIF1alpha/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS. CONCLUSIONS: Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1alpha/TWIST/E-cadherin pathway may play an important role in the progression of OEC.
Anoxia
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Cadherins
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Disease-Free Survival
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Epithelial-Mesenchymal Transition
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Immunohistochemistry
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Multivariate Analysis
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Prognosis
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Tumor Suppressor Protein p53
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Twist Transcription Factor
6.Different effects of several signal pathway after liver transplantation.
Guo-xun LI ; Nian-qiao GONG ; Qi-fa YE ; Hui GUO
Chinese Journal of Hepatology 2003;11(12):742-744
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
7.Investigation of p53 gene mutations in keloids using PCR-SSCP.
Yong-bo LIU ; Jian-hua GAO ; Hong-jie DUAN ; Xiao-jun LIU
Chinese Journal of Plastic Surgery 2003;19(4):258-260
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
8.Survival analysis of 118 chronic lymphocytic leukemia patients with abnormal TP53 gene in the era of traditional immunochemotherapy.
Xiao Tong LI ; Hua Yuan ZHU ; Li WANG ; Yi XIA ; Jin Hua LIANG ; Jia Zhu WU ; Wei WU ; Lei CAO ; Lei FAN ; Wei XU ; Jian Yong LI
Chinese Journal of Hematology 2019;40(5):378-383
Objective: To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT. Methods: The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β(2)-microglobulin (β(2)-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed. Results: Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β(2)-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn't receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences. Conclusion: CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.
Antineoplastic Combined Chemotherapy Protocols
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Female
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Genes, p53
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Humans
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Immunotherapy
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Leukemia, Lymphocytic, Chronic, B-Cell/genetics*
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Survival Analysis
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Tumor Suppressor Protein p53/genetics*
9.Expression of apoptosis-related proteins in gastric mucosa of children with Helicobacter pylori infection.
Wei-Ping LIU ; Su-Fang SUN ; Gui-Li ZHANG
Chinese Journal of Contemporary Pediatrics 2010;12(2):110-112
OBJECTIVETo investigate the relationship between apoptosis-related proteins in gastric mucosa, p53 and Bax, and Helicobacter pylori (H. pylori) infection in children.
METHODSp53 and Bax expression in gastric mucosa were measured using immunohistochemical technique in 33 children with gastric mucosal lesions. Presence/absence of H. pylori infection was detected by the rapid urease and pathological tests.
RESULTSFifteen children (88%) showed positive expression of p53 in 17 children who were confirmed with H. pylori infection, compared with 9 (56%) in 16 H. pylori negative children. Thirteen children (76%) showed positive expression of Bax in the 17 children with H. pylori infection, compared with 6 (38%) in the 16 H. pylori negative children. The expression levels of p53 and Bax in the H. pylori positive group were significantly higher than those in the H. pylori negative group (p<0.05).
CONCLUSIONSH. pylori infection is associated with the over-expression of p53 and Bax proteins in gastric mucosa in children.
Child ; Female ; Gastric Mucosa ; chemistry ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Humans ; Immunohistochemistry ; Male ; Tumor Suppressor Protein p53 ; analysis ; bcl-2-Associated X Protein ; analysis
10.Expression of Cyclooxygenase-2, p53 and Ki-67 in Gastric Cancer.
Young Eun JOO ; Ik Joo CHUNG ; Young Kyu PARK ; Yang Seok KOH ; Jae Hyuk LEE ; Chang Hwan PARK ; Wan Sik LEE ; Hyun Soo KIM ; Sung Kyu CHOI ; Jong Sun REW ; Chang Soo PARK ; Sei Jong KIM
Journal of Korean Medical Science 2006;21(5):871-876
It has been reported that p53 mutation may contribute to upregulate cyclooxygenase (COX)-2 expression that is observed in malignant tissues. These molecules are involved in carcinogenesis by affecting tumor cell proliferation. The aim of this study was to examine the relationship between COX-2 or p53 expression and clinico-pathological characteristics including tumor cell proliferation in gastric cancer. COX-2 and p53 expressions were investigated with immunostaining, in tissue specimens obtained from 119 patients who underwent surgery for gastric cancer. The Ki-67 labeling index (LI) was counted by Ki-67 immunostaining. COX-2 and p53 expressions correlated significantly with depth of tumor invasion. However, there was no association between COX-2 or p53 expression and survival. p53 expression did not correlate with COX-2 expression. There was no significant difference in various clinicopathological variables between Ki-67 LI subgroups. The mean Ki-67 LI value of COX-2 positive tumors was significantly higher than that of negative tumors. The mean Ki-67 LI value of p53 positive tumors was not significantly higher than that of negative tumors. The mean Ki-67 LI value of both COX-2 and p53 positive tumors was significantly higher than that of both negative tumors. These results imply that COX-2 expression is associated with tumor cell proliferation of gastric cancer.
Tumor Suppressor Protein p53/*analysis
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Stomach Neoplasms/*chemistry/mortality/pathology
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Prognosis
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Middle Aged
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Male
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Ki-67 Antigen/*analysis
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Immunohistochemistry
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Humans
;
Female
;
Cyclooxygenase 2/*analysis
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Aged
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Adult