Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The allele constitution at codon 72 of the p53 gene (CGC-arginine or CCC-proline) plays a major role in inducing apoptosis in p53 mutant cells. To verify this, we determined GC-status, p53-mutations, and p53-loss of heterozygosity (LOH) in a group of 54 squamous cell carcinomas of the head and neck (SCCHN). A novel approach, using a one-step real-time PCR analysis with fluorescent hybridization probes, was applied to detect the GC status in tumors and corresponding blood samples. p53 mutations in exons 4 to 8 were detected by PCR-SSCP-sequencing analysis. Apoptosis was determined immunohistochemically using antibodies against Fas, FasL, p53, Bcl2, and terminal deoxy-transferase-mediated dUTP nick end labeling (TUNEL) staining. The overall frequency of p53-LOH in SCCHN was 45.2%. In cases of LOH, there was a preferential loss of the proline allele, which was associated with an up-regulation of Bcl2 and lack of co-expression of Fas/FasL and, thus, impaired apoptosis (P < 0.001). Apoptosis was not observed in tumors carrying the arginine allele. p53 mutations were detected in 29.6% of SCCHN and preferentially occurred at the arginine allele (P = 0.01). p53 alterations were more frequently observed in tumors of the oral cavity, oropharynx and hypopharynx, whereas they were rare in larynx carcinomas (P = 0.07). The p53-LOH status was not found to be significantly correlated with sex, age, TNM-status, or tumor grading. We conclude that apoptosis is correlated with the allelic status of codon 72 in SCCHN. Homozygous proline 72 appears to be an important regulator of apoptosis via the Fas/FasL pathway in SCCHN.
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PMID:Retention of the arginine allele in codon 72 of the p53 gene correlates with poor apoptosis in head and neck cancer. 1503 12

Gallbladder cancer (GBC) is the most common biliary tract malignancy. There is a tremendous regional variability in its incidence. Risk factors include genetic susceptibility, gender, presence of gallstones, chronic biliary infections, diet and some anatomical anomalies. Several genetic abnormalities have been described which may be aetiologically important as well as carry prognostic significance. These include mutations in the proteins K-RAS and P53, and altered expression of P-glycoprotein, COX-2 and epidermal growth factor receptor. Most patients present at an advanced stage, overall prognosis is very poor. TNM stage and the extent of surgical resection are the most important prognostic factors. Surgery is the only curative therapy reserved for patients with early-stage disease. The role of adjuvant therapy is not fully defined. Patients with advanced disease are managed with systemic chemotherapy that is primarily palliative. Although 5-fluorouracil alone, or in combination, has been most commonly utilised, there is much greater enthusiasm for the combination of cisplatin and gemcitabine. The availability of better drugs and combinations may affect the use of chemotherapy in neoadjuvant and adjuvant settings. Novel targeted therapies require exploration alone or in combination with chemotherapy.
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PMID:Gallbladder cancer: current status. 1516 72

The aim of this study was to clarify whether specific p53 mutations may have biological relevance in terms of disease relapse or death in gastric carcinomas (GC). Resected specimens from a consecutive series of 62 patients with GC undergoing potentially curative surgery were prospectively studied. The mutational status of exons 5-8 of the p53 gene was investigated in 62 cases using the PCR-SSCP and sequencing. Presence of microsatellite instability (MSI) was evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%) occurred in highly conserved domains. According to the p53 specific functional domains: 4/20 mutations (20%) were in the L3 loop and 3/20 (15%) in LSH motif. Eight of the 56 GC resulted MSI-H, 5 (9%) MSI-L, and 43 (77%) MSI stable (MSS). None of the 8 (14%) MSI-H GC showed p53 mutations. p53 mutations were associated with intestinal histotype. Moreover, specific mutations in functional domain (L3 and LSH), together with advanced TNM stage, node involvement, depth of invasion, diffuse histotype, proved to be significantly related to quicker relapse and to shorter overall survival. Specific mutations in p53 functional domains, rather than any mutations in this gene, may be biologically more significant in terms of patients outcome, indicating that these mutations might have biological relevance to identify subgroups of patients at higher risk of relapse or death who might benefit from a more aggressive therapeutic approach.
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PMID:TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding domains of TP53 predict poor outcome. 1525 76

The biologic behavior of and optimal treatment for oral verrucous carcinoma (VC) remain controversial. We analyzed the clinicopathological characteristics of 12 patients with oral VC. Immunohistochemical techniques were used to evaluate p53 protein, CD44 variant 9, and proliferating cell nucleus antigen. The TNM classification (UICC, 1997) was T1 in 1 patient, T2 in 3, T3 in 4, and T4 in 4. All patients were classified as N0M0. Four patients were treated by surgery alone and 8 by surgery after chemotherapy, radiotherapy, or both. After surgery, two patients had primary recurrence of disease. Immunohistochemically, the proliferative activity of tumor cells as evaluated by proliferating cell nuclear antigen labeling index and p53 protein expression was similar in VC and well-differentiated squamous cell carcinoma. However, CD44 varient 9 expression was positive in 8 of 10 VC, suggesting that oral VC is associated with a low risk of lymph node metastasis. Positive CD44 variant 9 expression by most oral VCs, indicating a low risk of cervical lymph node metastasis, suggests that most cases can be controlled by surgical intervention.
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PMID:Treatment results of oral verrucous carcinoma and its biological behavior. 1528 33

To clarify the significance of p150 expression, 102 gastric carcinomas were immunohistochemically investigated and 14 fresh samples of the cancer were analyzed with the immunoblot method. Tumor cell apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL). Both Ki-67 antigen and p53 expression were analyzed immunohistochemically. Eighty-six out of 102 (85%) gastric cancers stained positively for p150. All 14 tumors analyzed by Western blotting overexpressed p150. Statistical analysis revealed a close association between p150 overexpression and the clinicopathologic parameters of gastric cancer. All well-differentiated cancers showed high p150 expression (p < 0.005). Furthermore, high p150 expression was more frequently seen in tumors at early invasive stages (p < 0.005), in tumors without metastases (both local and distant, p < 0.005) and in early TNM stages (p < 0.005) in general. As we have found for cervix and esophagus carcinoma, when tumors progress to high malignancy and metastasis, p150 begins to regress and then breaks down. A good correlation of p150 expression, but not p53 expression, with tumor cell apoptosis could be demonstrated (p < 0.01). The Ki-67 labeling index, i.e., the index for a proliferative marker, showed no correlation with either p150 or p53 expression. The results suggest that p150 may be a new early tumor marker for gastric carcinoma similar to that for esophagus and cervix carcinoma.
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PMID:p150 overexpression in gastric carcinoma: the association with p53, apoptosis and cell proliferation. 1538 63

Mutation of p53 is a common event in colorectal cancer and can result in cellular accumulation of p53 protein and induction of p53 antibodies. We investigated the association of colorectal cancer with alterations in p53 DNA, protein and serum antibody levels to determine their prognostic value in colorectal cancer. Colorectal cancer patients (n=167) who underwent surgery in Taipei Veterans General Hospital from January 1999 to December 2000 were enrolled [age 62.91+/-12.61 years (range: 22-85); 111 (66.5%) males]. Of these, 20 were stage I (12%), 54 stage II (32.3%), 58 stage III (34.7%), and 35 stage IV (21%). Median follow-up was 36.3 months (range: 4-58). p53 alteration was detected by DNA sequencing from exon 5 to 9 and loss of heterozygosity (LOH) at two microsatellite markers near p53; and demonstrating intratumoral accumulation of p53 protein and detection of serum p53 antibodies using ELISA. p53 mutation frequency was 41.9% (70/167). Of 127 informative cases for LOH analysis, 73 (57.5%) tumors that had LOH had at least one microsatellite marker. Genetic p53 alterations were found for 56.3% of cases when LOH and DNA sequencing methods were combined. Genetic p53 alterations were associated with advanced tumor stage and tumor differentiation. Overexpression of intratumoral p53 and anti-p53 antibody positivity were 44.9% and 28.1%. The presence of p53-Ab was associated with p53 mutations (chi2 test, 42.9% vs. 17.5%, p=0.001), but not with overexpression of intratumoral p53 protein. The mutations at exon 6 (57.1%) and 7 (53.3%) were associated with presence of serum p53-Ab. Of 132 potentially cured patients, 3-year disease-free survival (DFS) was affected by: advanced TNM stage (I, II, III: 90%, 84%, and 41%), genetic p53 alteration (89% vs. 43%), intratumoral p53 accumulation (71% vs. 56%), and preoperative CEA level >5 ng/ml (74% vs. 58%). In multivariate analysis, genetic alteration of p53 was the most significant independent prognostic factor [hazard ratio (HR) = 6.09; 95% confidence interval (CI): 2.45-15.11], followed by advanced tumor stage (HR = 3.93; 95% CI: 2.14-7.23), and preoperative CEA >5 ng/ml (HR = 1.98; 95% CI: 1.12-3.17). Genetic alterations in p53 but not intratumoral p53 protein accumulation or p53-Ab appear to play a significant role in the progression of colorectal cancer.
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PMID:Genetic alteration of p53, but not overexpression of intratumoral p53 protein, or serum p53 antibody is a prognostic factor in sporadic colorectal adenocarcinoma. 1558 26

The difficult cancer development and the insufficient knowledge of the biology of the existing cancers lead for the constant search for the new techniques of diagnosis. The aim of this study was to analyze the selected prognostic factors such as p53, Ki67 and cyclin D1 in patients with head and neck cancer in connection with histological differentiation (G), TNM classification and the clinical advancement of the disease (S). The material comprised of the tissue specimens from 32 patients with squamous cell carcinomas of head and neck, who underwent the primary surgery. The immunohistochemical study was performed with avidin-biothin method. A 5-point grading system was adopted to assess the level of the immunohistochemical staining of the carcinoma cells. Through our study we found a statistically significant correlation between the staining intensity of carcinoma cells for p53, Ki67, cyclin D1 and the TNM classification and the clinical advancement of the disease (S). Such correlation for the histological differentiation (G) has not been observed. We think that the immunohistochemical techniques may constitute an important supplement of evaluation of the malignancy in the squamous cell carcinomas of head and neck.
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PMID:[Ki67, p53 and cyclin D1 in the squamous cell carcinoma of head and neck]. 1560 89

Many factors affect the prognosis in operable laryngeal squamous cell carcinoma (LSCC). Many clinical factors have been implicated in tumor recurrence and poor survival of the patients. The aim of the present study is to investigate the demographic, clinical and histological characteristics as prognostic factors. Moreover, our aim is to analyze the role of modern molecular biomarkers in the prognosis of patients with LSCC. One hundred patients with operable laryngeal carcinoma underwent surgery as primary treatment between April 1999 and April 2002. Ninety-four of them were men and 6 women, with a median age of 62 years (39-77). All demographic data of the patients were recorded. Staging of the tumor revealed 20 cases with T2 cancer, 46 cases with T3 and 34 cases with T4, while N classification included 91 patients with N0 tumor, 3 with N1 and 6 with N2. Among the 100 cases, 47 were located in the glottis, 46 in the supraglottic region and 7 were transglottic. Histology grading revealed 35 cases of grade G1, 50 cases of G2 and 15 cases of G3. Postoperatively, all patients were followed regularly for the possibility of tumor relapse, with a median follow-up period of 40.2 months (4.8-58.4). During the operation, a tissue specimen was collected from the tumor. The specimens were used for RNA and DNA extraction. Isolated RNA was used to investigate the expression of wt-p53, bcl-2, VEGF and EGFR by the reverse transcriptase PCR method (RT-PCR) using specific primers, while genomic DNA was used for the detection of EBV and HPV (16/18 subtypes) by the consensus primer-mediated polymerase chain reaction method (PCR). All data such as tumor recurrence and survival were recorded. Statistical analysis was performed using the SPSS and STATA statistical packages in order to investigate the role of all clinical and molecular factors and their combinations as significant prognostic markers. The tumor recurrence rate was 31%, while the tumor associated death rate was 27% and total death rate 30%. Univariate analysis for overall survival showed significance for the T stage, TNM stage and site of the tumor. Univariate analysis for the time to progression showed significance for the T stage, N stage, TNM stage, site of the tumor and tumors simultaneously positive for EGFR and VEGF, while EGFR expression was borderline insignificant. Multivariate analysis revealed TNM stage as the only significant factor for overall survival, and TNM stage, site of the tumor and EGFR expression as significant factors for time to progression. The molecular biomarkers EGFR and VEGF have a prognostic significance in laryngeal cancer in addition to the established clinical prognostic factors such as the stage and site of the tumor. These markers, apart from their role in carcinogenesis, seem to play an important role in tumor relapse.
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PMID:Clinical and molecular prognostic factors in operable laryngeal cancer. 1573 81

The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.
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PMID:Cyclooxygenase-2 and p53 expression as prognostic indicators in conventional renal cell carcinoma. 1574 16

Mammary serpin (Maspin) belongs to the serine protease inhibitor (serpin) superfamily and has been identified as a tumor suppressor. In addition, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. The role of maspin in the tumorigenesis and progression of colorectal cancer is still unclear. Therefore, the first aim of the present study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of patients with colorectal carcinoma undergoing left- or right-sided colectomy. Secondly, maspin expression was correlated with p53 protein expression to gain additional information about a possible regulatory influence of the wild-type p53 protein on maspin; it was also correlated with further patient and tumor characteristics (age, sex, TNM, disease stage, tumor localization, and grading). An immunohistochemical study was performed on 280 carcinoma specimens using the tissue microarray technique. In addition, 80 colorectal adenomas and 60 tumor-free tissues were investigated. Maspin protein expression was detectable in 88-100% of the adenomas and non-tumorous tissues and in 193 out of 280 carcinoma patients (69%; maspin-positive). After a median follow-up of 102 months (23-140 months), the median recurrence-free survival was 80 months for maspin-positive cases (M +) and 42 months for maspin-negative cases (M-) (p = 0.02). The median long-term survival was 98 months for M + and 57 months for M- (p = 0.03). After 5 years, M + and M- patients had a total survival of 69% and 38%, and, after 10 years, 45% and 9%, respectively. Mutant type p53 expression was detectable in 178 colorectal carcinomas (64%). Mt p53 was positive in 91 out of 193 M + (47%) compared with 87 of 87 M- (100%, p<0.001). This study showed that loss of maspin protein correlates with p53 protein activity, with a higher likelihood for the development of tumor relapse, and with a decreased recurrence-free and overall survival in colorectal carcinomas. The determination of the immunohistochemical expression status of maspin might be a helpful independent prognosticator and an applicable tool for the development of therapeutic strategies for patients with this disease.
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PMID:Loss of maspin is a helpful prognosticator in colorectal cancer: a tissue microarray analysis. 1579 21


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