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)

Observations support the theory that development of left- and right-sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2, p53, E-cadherin and beta-catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear beta-catenin expression (p=0.75). Rectal cancers showed significantly more nuclear beta-catenin than colon cancers (65% versus 40%, p=0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry (p<0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p=0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease-free survival (p=0.008), but not in colon cancers. Cox regression showed that p53-expression (p=0.03) was an independent predictor for disease-free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear beta-catenin in the APC/beta-catenin pathway than colon cancer and/or nuclear beta-catenin may have another role in rectal cancer independently of APC. The p53-pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered.
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PMID:Mechanisms of oncogenesis in colon versus rectal cancer. 1159 95

Tumours of patients with node-positive rectal cancer were studied by immunohistochemistry for p53, BAX and vascular endothelial growth factor expressions. Results were correlated to the relapse rate, the pattern of relapse and the event-free survival after radical surgery and adjuvant chemoradiation. After a median follow-up of 60 months, 39 patients remained disease-free and 40 patients relapsed (18 local relapses and 22 distant metastases). The majority of disease-free patients showed p53 negative and vascular endothelial growth factor negative tumours. Local relapses occurred more frequently in patients with p53 overexpressing tumours (P<0.01), while distant metastases were in patients with vascular endothelial growth factor positive tumours (P<0.003). Patients with p53 negative or vascular endothelial growth factor negative tumours showed better event-free survival than patients with p53 positive or vascular endothelial growth factor positive tumours. BAX analysis did not show any association with patients' outcome and it was unrelated to the p53 status. Adjuvant treatment strategies for node-positive rectal cancer may be improved by identifying categories of high-risk patients. In this study, vascular endothelial growth factor and p53 expressions correlated with recurrent disease, pattern of relapse and poor event-free survival.
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PMID:An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation. 1187 37

The influence of p53 mutations on the response to ionizing radiation and survival was retrospectively evaluated in patients treated with preoperative radiotherapy for rectal carcinoma. From 1989 to 1991, 86 rectal cancer patients treated by preoperative radiotherapy were included in this series. For all patients, endorectal sonography (to define ultrasonography TNM [uTNM]) was performed before treatment; 19 patients were classified as stage 1, 27 as stage 2 and 40 as stage 3. Response to radiotherapy (39 Gy in 13 fractions delivered in 17 days) was assessed by comparing the uT and the T obtained by histologic examination of the resected specimen (TNM classification). A rectal cancer biopsy was performed before treatment and enabled the search for p53 mutations by denaturing gradient gel electrophoresis (DGGE) and sequencing. The status of the p53 gene was correlated with the response to radiotherapy and survival. Forty-nine percent of the tumors presented abnormal DGGE profiles. The prevalence of p53 mutations was significantly higher in patients who did not respond to radiotherapy (63%) than in those who did respond (34%) (p < 0.01). Presence of a p53 mutation was associated with significantly shorter 5-year survival compared to patients without mutations (p < 0.02). In a multivariate analysis, p53 mutation status remained a prognostic factor independent of tumor posttreatment staging (p < 0.05). p53 status is an independent prognostic factor of response to radiotherapy and survival in rectal carcinoma.
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PMID:Prognostic value of P53 mutations in rectal carcinoma. 1211 59

Recent molecular biological studies suggested certain molecular markers might be useful as prognostic factors in patients with colorectal cancer. The purpose of this study was to investigate whether cyclin dependent inhibitor kinase p21WAF1/CIP1 (p21), p53 expression, and/or the presence of apoptosis had prognostic value in predicting survival in patients with advanced middle and lower rectal cancer who were treated with preoperative radio-chemotherapy. We examined the immunohistochemical expression of p21 and p53, and determined the degree of apoptosis in resected middle and lower rectal cancers from patients who received preoperative radio-chemotherapy (irradiation group, n=40) and from those who did not receive treatment (control group, n=35). The preoperative total radiotherapy dose was 42.6 Gy and the chemotherapy tegafur suppository dose was 750 mg/day. Clinicopathological features, and tumor expression of p53 and p21 and degree of apoptosis were analyzed by means of multivariate analysis. In the irradiation group, tumors were positive for p53, p21 and apoptosis in 34 of 40 (85.0%), 23 of 40 (57.5%) and 25 of 40 (62.5%) cases, respectively. The expression of p21 and the apoptotic index were significantly higher in the irradiated group compared to controls (2.0 versus 1.2%, p=0.05; 8 versus 3%, p=0.03, respectively). There was a significant correlation between p21 immunoreactivity and the degree of muscularis propria invasion (p=0.004), as well as between p21 immunoreactivity and survival rate (p=0.03). Multivariate analysis revealed that p21 expression (RR, 0.09; 95% CI, 0.01-0.78; p=0.03) and lymph node metastasis (RR, 3.63; 95% CI, 1.06-12.37; p=0.04) were significant prognostic factors for patient survival. These data suggested that p21 expression has prognostic value in predicting patient survival in advanced middle and lower rectal cancer.
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PMID:Value of expression of p21WAF1/CIP1 as a prognostic factor in advanced middle and lower rectal cancer patients treated with preoperative radio-chemotherapy. 1223 17

Topoisomerase I (topo I) is an important target for the treatment of malignant disease, especially colorectal cancer. Because there is little information on the expression of topo I in colorectal tumors, this study evaluated and characterized topo I protein expression in primary colorectal cancer and lymph node metastases and studied the association between topo I protein expression and clinicopathologic data, p53 status, and proliferating cell nuclear antigen (PCNA) status. Immunohistochemistry assay was performed for topo I protein expression in 249 primary human colorectal cancer and 42 paired lymph node metastasis samples. Topo I expression was described as the percentage of cells staining positive for topo I, along with the intensity and localization of the staining. Clinicopathologic data (sex, age, Dukes' stage, differentiation grade, survival status), p53 status, and PCNA status were statistically analyzed for association with topo I protein expression. Topo I expression in paired primary lymph node metastases were studied for concordance. Topo I protein expression was detected in 127 (51%) samples, including 24.4% with >50% positive tumor cells. The majority had nuclear (70.1%) or nuclear and cytoplasmic staining (17.3%). A higher percentage of cells expressing topo I in primary colorectal cancer was significantly associated with advanced age (P =.040). Patients with rectal cancer had greater topo I expression than those with colon tumors (P =.029). No significant correlation was found between topo I protein expression and sex, Dukes' stage, differentiation grade, survival status, p53 status, and PCNA status. Concordance in topo I staining between primary and lymph node metastases was observed in 33 of 42 cases (P =.029). This suggests that the activity of topo I inhibitors will not differ across various tumor stages, pathology, and patient gender. p53 and PCNA status do not appear to influence topo I expression, and topo I has no apparent association with the acquisition of a metastatic phenotype. Topo I expression now needs to be evaluated in patients undergoing topo I-inhibitor therapy, to better define the role of this protein as a predictive marker.
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PMID:Topoisomerase I protein expression in primary colorectal cancer and lymph node metastases. 1245 16

The most frequent form of neoplasia in the oral cavity is the squamous cell carcinoma (about 90% of cases) representing the 3-5% of all malignant tumors with about 56% of mortality rate, at 5 years from the diagnosis. In general, the neoplastic disease is now unanimly considered as a multifactorial and multiphasic pathology. Multiphasic since the carcinogenic process consists in the cellular capacity to acquire oncological potentialities through several stages such as: moltiplication (a), transmission (b) of malignity caracteristics to progenic cells, invasivity (c), capacity to give metastasis (d) and also resistance to chemiotherapy. Multifactorial since in the onset of the disease intrinsic and extrinsic factors are certainly involved. In the carcinogenic process of CCS a high percentage has been noticed of loss of heterozygosity (LOH) in the short arm (P) of cromosoms 3 and 9, which contains the tumor-suppressor genes p53 and DDC (Deleted in colon rectal cancer). In the onset of VADS carcinoma and in particular of oral CCS, it has also been formulated the hypothesis of an intrinsic genetic factor (Llewellyn et al., 2001) between patients, also young, who present the neoplasia even trough they have never been exposed to extrinsic risk factors such as smoke and alcohol. Since part of patients with oral CCS do not always refer a common risk factors history as possible extrinsic neoplasia causes, it has been formulated the hypothesis that some viral infections, for their oncogenic capacity, could be the main ethiological factors predisposing to this neoplasia. The HPV are responsible, either in the oral cavity or on the epidermis, for benign proliferations such as: Verruca Vulgaris, Condyloma Acuminatum, Focal Epithelial Hyperplasia, Squamous Cell Papillomas, but also lesions that are potentially or certainly malignant such as CCS and Verrucous Carcinoma. The molecular analysis performed show that proteins produced from E6 and E7 portions of viral genoma (HPV 16-18) interfer and degrade proteins p53 and pRb produced by tumor suppressor genes (TSg). Recently, thanks to new molecular biology techniques, several authors are studying potentially neoplastic lesions, in order to better understand the association with HPV.
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PMID:[Soft tissue pathologies of the oral cavity]. 1268 15

The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P = 0.045); Ku70 and tumor radiosensitivity (P < 0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.
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PMID:Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression. 1286 72

The aim of this study was to investigate the activation of the p53 pathway and the induction of apoptosis during preoperative radiotherapy in normal human rectal tissue and in rectal carcinoma. Twelve patients with rectal cancer of the lower third were enrolled in this study. Tumor specimens and adjacent normal tissue were obtained before radiation, after the third radiation cycle and from the surgically removed rectum. All specimens were analyzed be means of immunohistochemistry for expression of p53 and its downstream target genes MDM2 and p21. In normal mucosal crypts, irradiation led to p53 accumulation and MDM2 induction in more than 70% of the cells. The accumulation of p53 in basal crypts was associated with high expression of p21. Apoptosis was also induced in crypts and occurred in 15% of the cells. Activation of the p53 pathway was not seen in the resting cells at the luminal border of the epithelium. In interstitial cells, p21 was highly upregulated, whereas p53 and MDM2 showed weak expression. The level of bcl-2 was not altered during radiotherapy in healthy tissue. In rectal carcinoma cells, p53 expression was unaltered by irradiation in 11 out of 12 tumors. The p53 non-functional tumors were characterized by a weak induction of MDM2 and p21 and by the lack of apoptosis in the presence of bcl-2. Our findings demonstrate that sequential immunohistochemical analysis is suitable to detect a deregulation of the p53 pathway in human rectal cancer cells during radiotherapy. Further investigations are necessary to elucidate its value as a prognostic marker and potential predictor of therapy responsiveness.
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PMID:The early response of p53-dependent proteins during radiotherapy in human rectal carcinoma and in adjacent normal tissue. 1453 65

We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, E-cadherin, beta-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Immunostaining revealed frequent upregulation and/or aberrant staining patterns for several of the markers, but Ki-67, p53, Bcl-2 and EGFR did not show any correlation to prognosis. However, reduced membranous staining for beta-catenin (p = 0.04), lack of cytoplasmic staining for beta-catenin (p = 0.04), reduced membranous staining for E-cadherin (p = 0.02) and lack of cytoplasmic staining for E-cadherin (p = 0.02) correlated with metastatic disease. Multivariate analysis including the factors Dukes' stage and tumor differentiation grade demonstrated increased risk of metastatic disease in tumors with lack of cytoplasmic staining for beta-catenin (HR = 3.1, p = 0.02), reduced membranous staining for beta-catenin (HR = 1.7, p = 0.06) and reduced membranous staining for E-cadherin (HR = 2.1, p = 0.06). Loss of MMR protein expression was confirmed to be a rare event in rectal cancer with loss of MLH1 staining in 3% and MSH2 in 1% of the tumors. The lack of prognostic information contributed by most of these markers suggests that single markers for prognosis may be of limited value in rectal cancer. However, altered expression of beta-catenin and E-cadherin correlated with metastatic disease, and these markers may have prognostic importance in rectal cancer.
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PMID:Immunohistochemical patterns in rectal cancer: application of tissue microarray with prognostic correlations. 1530 Aug 4

We performed a systematic review of studies that investigated the effect of abnormalities of the tumour suppressor gene p53 upon prognosis in patients with colorectal cancer. The methods used to assess p53 status were immunohistochemistry (IHC), indicating abnormal accumulation of p53, and sequence analysis, indicating presence of p53 mutations (mut). We identified 168 reports, with 241 comparisons of relevant end points and survival data on 18 766 patients. We found evidence of both publication bias and heterogeneity of results. Our analysis was hampered by variability in both the assessment of p53 status and the reporting of results. We used a trim and fill method to correct for publication bias and minimised heterogeneity by using well-defined clinical subgroups for the assessment of outcomes. Overall, patients with abnormal p53 were at increased risk of death: relative risk (RR) with IHC 1.32 (95% confidence interval (c.i.) 1.23-1.42) and with mutation analysis 1.31 (95% c.i. 1.19-1.45). The adverse impact of abnormal p53 was greater in patients with lower baseline risk of dying: good prognosis RR (mut) 1.63 (95% c.i. 1.40-1.90) and poor prognosis RR (mut) 1.04 (95% c.i. 0.91-1.19). We found no effect of abnormal p53 on outcome in patients treated with chemotherapy. Abnormal p53 was associated with failure of response to radiotherapy in patients with rectal cancer: RR (mut) 1.49 (95% c.i. 1.25-1.77).
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PMID:P53 abnormalities and outcomes in colorectal cancer: a systematic review. 1585 32


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