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 ability of cancer cells to metastasize might depend on their reduced dependency on the originating tissue. To test this hypothesis, 10 human colorectal carcinomas (CRC) were implanted either onto nude mouse caecum wall (orthotopic site), or into the subcutaneous tissue (ectopic site), and their growth in these sites compared. Prognostic factors were studied: Astler-Coller modified Dukes's stage, loss of chromosome 17p and/or 18q, and their TP53 gene. Early stage CRC [B2 (n = 3) and C1 (n = 1)] were found to grow 1.7 to 3.6 times (p < 0.05, p < 0.008 respectively) more rapidly in the caecum than in subcutaneous tissue. Metastatic stage CRC [C1 (n = 1), C2 (n = 2) or D (n = 3)] grew similarly in both sites, and more slowly than those of the first group. No relationship was found between growth rates, TP53 mutations or karyotypes. Growth rate of non metastatic cancers was slowed down by implantation in a foreign tissue whereas growth of metastatic tumours was similar in both sites, indicating that they do not recognize or need tissue growth factors.
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PMID:Growth dependency of human colon cancer xenograft on organ environment is related with their original clinical stage. 970 39

The expression of ras was investigated by using immunohistochemistry in 245 primary colorectal adenocarcinomas and 49 corresponding metastases in the lymph nodes. One hundred and forty-four (59%) of the primary tumours presented as ras positive and 37 (76%) were positive in metastases. The ras expression was positively related to cell proliferation (p=0.01) and significantly increased in tumours with aneuploidy (68%) compared to tumours with diploidy (51%) and tetraploidy (53%, p=0.01). The frequency of ras expression was increased from Dukes' stage A to stages B-D (41% vs 62%, p=0.01). ras expression was compared in 40 paired primary tumours and their corresponding metastases, and the difference in expression did not reach statistical significance (73% vs 83%, p=0.32). In survival analyses, ras overexpression predicted a poor prognosis independent of Dukes' stage, DNA ploidy and S-phase fraction (p=0.049). We did not find any significant relationship between ras expression and patients' sex, age, tumour location, growth pattern, differentiation, p53 expression or heat shock protein. The results indicate that the alteration of ras expression may be involved in the instability of DNA and cellular overproliferation, but not in the progression to advanced stage and the development of metastases. The expression of ras was an important biological marker for evaluating the prognosis in patients with colorectal adenocarcinoma.
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PMID:Overexpression of ras is an independent prognostic factor in colorectal adenocarcinoma. 972 99

The incidence of non-familial multiple primary cancer in colorectal cancer patients has increased in recent years in Japan. To clarify the characteristic genetic aberrations in such multiple cancers, we examined structural chromosomal aberrations by fluorescence in situ hybridization, using chromosome 17-specific and p53 cosmid DNA probes. We established short-term cultures of 78 surgical specimens and were able to obtain observable metaphase spreads in 23 single colorectal cancer specimens and in 6 colorectal cancer specimens from patients with double primary cancers. The frequency of chromosome 17 and/or p53 locus translocation was significantly greater in tumors with double cancer than in single colorectal cancers (P < 0.05 and P < 0.01, respectively). These aberrations in double cancers frequently appeared even at an early Dukes' stage (A and B) of colorectal carcinoma. Our results suggest that translocation of chromosome 17 and the p53 locus may be specific genetic events probably associated with carcinogenesis of multiple primary cancers in colorectal cancer.
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PMID:Importance of cytogenetic markers for multiple primary carcinomas in colorectal cancer: chromosome 17 and p53 locus translocation. 977 31

Alterations of the p53 gene and the p53 protein are common in a wide spectrum of human malignancies. In several tumor types, p53 gene mutation and/or p53 protein overexpression correlate with a more clinically aggressive phenotype as judged by worse patient survival. This has not been clearly demonstrated to be the case in colorectal cancer. Herein, we report results of the prognostic significance of p53 protein accumulation and gene mutation in a large series of colorectal cancers (n = 541) with long patient follow-up (mean, 87 months). The large majority of patients (95%) received no postoperative systemic adjuvant therapy. The incidence of p53 accumulation detected by immunohistochemistry with the monoclonal antibody DO-7 was 30%, whereas the incidence of p53 gene mutation in exons 5-8 detected using PCR-single strand conformation polymorphism was 36%. Accumulation of p53 protein was associated with improved patient survival independent of tumor stage or grade (hazard ratio, 0.66; 95% confidence interval, 0.47-0.93; P = 0.017). A marked difference was observed depending on the location of the tumor: tumors originating in the distal colon showed a strong association between the presence of p53 accumulation and improved patient survival (P = 0.003), but this was not the case for those located in the proximal colon. Dukes' stage C tumors, but not stage B, also showed an association between p53 accumulation and better outcome (P = 0.013). Mutation of the p53 gene was associated with a trend toward improved survival, particularly in the distal tumors. Our results demonstrate that in some tumor types, the presence of p53 abnormalities can correlate with better prognosis.
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PMID:p53 alterations are associated with improved prognosis in distal colonic carcinomas. 981 25

L-myc genotypes have been correlated with prognosis in different human tumors. Its role in colorectal carcinoma (CRC) is still unclear. This study aimed to assess the L-myc genotypes in 99 Hong Kong Chinese CRC patients by PCR-RFLP techniques. The results obtained were correlated with clinical, histological and pathological parameters and genetic alterations. The observed frequency of L-myc genotypes (LL:LS:SS) was 27:46:26. The ratio of S to L alleles was 0.51:0.49. Distribution of L-myc genotypes and alleles in Hong Kong Chinese CRC was similar to that of healthy Chinese and CRC patients of other ethnic origins. The homozygous SS genotype was significantly associated with Dukes' stages C versus B. Other parameters including sex, differentiation status and survival, and genetic alterations such as p53 and Ki-ras mutations and Dcc LOH had no significant association with L-myc SS genotype.
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PMID:L-myc genotypes in Hong Kong Chinese colorectal carcinoma patients. 1002 18

Background: Topographic genotyping is a system of solid tissue molecular analysis designed to correlate microscopic alterations with specific forms of gene damage. In this system, microscopic targets are selected on the basis of cellular and immunohistochemical features. Minute tissue samples corresponding to these targets are precisely removed and analyzed for the presence and specific type of oncogene/tumor suppressor gene damage by means of polymerase chain reaction (PCR) followed by DNA sequencing. In this study, topographic genotyping was used to investigate the prognostic value of p53 and K-ras-2 mutational damage in 204 patients with colorectal cancer from two tertiary care centers. Methods and Results: The intensity and distribution of p53 immunohistochemical staining were correlated with the presence and specific type of mutational change, which resulted in a better understanding of the highly variable nature of p53 immunostaining patterns. Molecular genotype was correlated with the depth and extent of colorectal cancer spread (Dukes B and C) and with survival for follow-up periods of up to 10 years. An algorithm for p53/K-ras-2 genotyping was formulated to include p53 immunohistochemistry and DNA sequencing both of p53 exons 5-8 and of K-ras-2 exons 1 and 2. By using this algorithm, survival was shown to be significantly better in those patients whose tumors manifested normal p53 and K-ras-2 genes (P >.01). Patients with p53-mutated tumors composed a poor prognostic group, characterized by a high rate of intra-abdominal recurrence in the form of peritoneal seeding. Patients with K-ras-2-mutated tumors also composed a poor prognostic group, marked by a tendency for distant hematogenous metastasis involving lung, bone, and brain. Conclusions: Topographic genotyping's molecular diagnostic approach to colorectal cancer combines immunohistochemistry, PCR, and DNA sequencing. It is informative, cost-effective, timely, and yet fully integrated with standard histopathology. The use of this approach by pathologists as a model system for molecular diagnosis of colorectal cancer and other forms of solid tumor malignancy is recommended. As new prognostic molecular lesions are documented for tumor progression and metastasis, topographic genotyping will be well suited to facilitate their clinical application.
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PMID:Prediction of Biologic Aggressiveness in Colorectal Cancer by p53/K-ras-2 Topographic Genotyping. 1033 Jan 94

We investigated the clinicopathological and genetic characteristics including patients' gender, age, tumour location, growth pattern, Dukes' stage, DNA ploidy, S-phase fraction, PCNA, apoptosis, c-erbB-2, bcl-2, K-ras, p53, DCC and heat shock protein in 32 mucinous carcinomas versus 261 non-mucinous carcinomas in the colorectum. Sixty percent of mucinous carcinomas were located in the right colon, 13% in the left colon and 27% in the rectum (p=0.01). More mucinous carcinomas grew in expanding pattern than non-mucinous carcinomas (66% vs 39%, p=0.005). Compared with non-mucinous carcinoma, mucinous carcinoma had more K-ras mutations (50% vs 25%, p=0.02), but less p53 expression (72% vs 49%, p=0.02) and less apoptotic activity (19% vs 51%, p=0.01). We further confirm that the mucinous carcinoma in the colorectum represents a distinct clinicopathologic and genetic features as compared to non-mucinous tumour, and may have a different biological behaviour.
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PMID:Clinicopathological and genetic characteristics of mucinous carcinomas in the colorectum. 1033 57

We have analyzed the loss of heterozygosity (LOH) of TP53 in a series of 96 sporadic colorectal carcinomas by means of PCR, using two microsatellite sequences (TP53 and Mfd152), to investigate its possible relationship with several clinicopathological variables in the Spanish population. Forty six of the 96 patients (48%) showed loss of one allele of the microsatellite TP53, Mfd152 or both, when compared with normal colorectal mucosae and blood samples of the same patient. This high percentage of LOH seems to corroborate the important role of p53 in sporadic colorectal cancer. However, we have found that LOH on this region is independent of histological grade and tumour location. With regard to tumour Dukes' stage, the fact that a substantial proportion of tumours show LOH on 17p from the first stages of the disease could imply that this alteration is not related with the invasiveness acquisition staging.
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PMID:Loss of heterozygosity of TP53 is not correlated with clinicopathological variables in sporadic colorectal carcinomas. 1036 94

Colorectal cancer is a disease that is associated with default in the balance of apoptotic regulation. In the present study apoptosis was examined in 158 colorectal adenocarcinomas using the terminal deoxynucleotidyl transferase mediated digoxigenin nick end labeling (TUNEL) method. The median apoptotic index (AI) was 0.95% (range 0-6. 68%). Eighty-two tumours exhibited AI </=0.95% and 76 tumours showed AI >0.95%. We revealed a positive correlation between apoptosis and proliferation determined as the expression of proliferating cell nuclear antigen (PCNA, p=0.002). The frequency of apoptosis increased from Dukes' stage A, B, C to D (p=0.01). No correlations were found between apoptosis and the patients' sex, age, tumour location, growth pattern, differentiation, prognosis, bcl-2, p53 or K-ras. Our findings suggest that we should further investigate the relationship between apoptosis and cellular proliferative activity in colorectal cancer to evaluate whether this might provide additional information in the selection of patients for effective adjuvant therapy.
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PMID:Apoptosis in relation to proliferating cell nuclear antigen and Dukes' stage in colorectal adenocarcinoma. 1037 93

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.
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PMID:Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas. 1038 39


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