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)

Serum autoantibodies against the p53 protein (p53 AAb) were analysed with a newly developed enzyme-linked immunosorbent assay (ELISA) based on highly purified and renatured p53. In a hospital-based cohort study, preoperative sera from 113 patients with ovarian cancer, 15 patients with borderline tumours and 117 patients with benign tumours of the ovaries were studied. The prevalence of p53 AAb in patients with invasive cancer was 19% (21/113). No p53 AAb were found in patients with borderline lesions or benign tumours. The ELISA had a specificity for malignancy of 99% (1 of 117; false-positive from a patient with severe diabetes mellitus) and a likelihood ratio (LR+) for a positive test result of 21.7 (elevated CA125 and malignancy: LR+ 3.7). p53 AAb were only detectable in patients with immunohistochemical staining of nuclear p53 in the tumour (P = 0.006). Presence of p53 AAb positively correlated with tumour stage (P = 0.034) and grade (P = 0.009). Kaplan-Meier analysis showed both a shortened overall survival (P = 0.0016, log-rank) and relapse-free survival (P = 0.055) for p53 AAb-positive patients (median follow-up 22 months). High titres related to even worse prognosis. p53 AAb independently related to poor survival adjusting for stage (P = 0.026), grade (P = 0.029) and residual disease after surgery (P = 0.005). Preoperative findings of adnexal mass with serum p53 AAb are strongly suggestive of an aggressive invasive ovarian cancer.
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PMID:Autoimmunity against p53 predicts invasive cancer with poor survival in patients with an ovarian mass. 1104 59

Five cases of urachal carcinoma experienced in our hospital during the past 20 years are reported. Surgical resection is considered as the first treatment option of this disease, and other therapies to be less beneficial. Complete surgical extirpation and detection of recurrence in the early stage are considered to be important since local recurrence occurs frequently. We enforced the bladder preserving operation for 4 patients with urachal carcinoma except for 1 case with peritonitis carcinomatosa in the initial diagnosis, and multiple surgical treatment was performed again for 2 patients with recurrence. The bladder was preserved with no evidence of malignancy in three patients for 24, 19 and 5 years, respectively. In the initial management of urachal carcinoma, we believe that bladder-preserving surgery should be considered in selected cases though close follow-up is demanded. Herein, we also report the immunohistochemical study of paraffin-embedded specimens using anti-CEA, CA19-9, CA125 and p53 monoclonal antibodies. The positive reaction was observed in 100% (5/5) for CEA, 80% (4/5) for CA19-9, and 20% (1/5) for CA125. These results suggest that CEA may be a useful marker in the diagnosis of this neoplasm and early detection of its recurrence. Nuclear accumulation of p53 was observed in 80% (4/5), but it did not correlate with the disease progression.
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PMID:[Long-term clinical results of 5 cases of urachal carcinoma]. 1121 96

Mutations of the p53 tumour suppressor gene have been found in most human cancers, including ovarian epithelial malignancies. This study investigated whether the presence or absence of p53 mutation was associated with outcome following platinum-based chemotherapy in patients with ovarian cancer. DNA samples from tumour tissue and blood were obtained from 73 patients with primary tumours, 50 of whom received platinum-based adjuvant chemotherapy. Single-strand conformation polymorphism analysis and direct DNA sequencing of exons 5-8 detected mutations in 44% (32 of 73) of tumours. These were more common in late-stage (III or IV) than in early-stage disease (I or II) (p=0.03). There was no association with histological type, volume of residual disease following surgery, or initial CA125 levels. No significant association was found between p53 status and overall survival or disease-free survival following chemotherapy. Likewise, there was no correlation between p53 mutation and response to chemotherapy as defined by normalization of CA125 levels. Tumours with p53 missense mutations recurred within a significantly shorter time than those with normal p53 (p=0.04). In addition, there was a tendency for tumours with missense mutations to have a shorter disease-free survival than those with non-missense mutations, although this did not reach statistical significance (p=0.07).
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PMID:P53 mutation does not affect prognosis in ovarian epithelial malignancies. 1132 43

Reports of supernumerary ovaries are rare. We describe two such cases, one with fibroma and the other with endometriosis and cystic change. A large fibroma measuring 17.4 x 12.0 x 7.5 cm in size was found in the supernumerary ovary of the omentum in the first case of a 47-year-old married woman with Meig's syndrome. The second case was associated with endometriosis and cystic change, measuring 11 x 5 x 3 cm in size and located in the upper abdominal cavity. It was attached to the uterus of a 28-year-old pregnant woman who had neither fibroma nor Meig's syndrome. Histologically, corpus albicans and a few primordial germ cells were demonstrated, respectively. A fibroma showing a storiform pattern was found in the first case. The second case had endometriosis and a thin-walled cyst with bleeding and necrosis caused by torsion. Immunohistochemically, desmin, alpha-smooth muscle actin, c-kit, CA125, Na+/K+ATPase, overexpression of p53, myc and ras were all negative in the fibroma cells of the first case, and in the endometriosis and cyst wall of the second case. The fibroma cells were positive for vimentin and estrogen receptor, and the proliferating cell nuclear antigen was sporadically demonstrated in their nuclei. The mutation of the p53 gene at exons 5-8 was not detected by sequence analysis. Using RT-PCR, bax, bcl-2 and p16 were not detected either. Clinically, the two cases presented here did not show abnormal hormonal symptoms. They were diagnosed as abdominal tumors or masses. Based on these considerations, one might assume that supernumerary ovaries are probably more frequent than reported at present.
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PMID:Two cases of supernumerary ovary: one with large fibroma with Meig's syndrome and the other with endometriosis and cystic change. 1179 34

The p53 gene, a tumour suppressor gene located on the short arm of chromosome 17 (17p13), is frequently mutated in various human tumours. Accumulation of p53 protein in neoplastic cells and its release following tumour necrosis can lead to development of circulating autoantibodies (AAb) against p53. Earlier studies of ovarian cancer (OC) patients reported different frequencies of p53 AAb and conclusions regarding the clinical and prognostic value of these AAb have not been in agreement. We therefore analysed for the presence of p53 AAb in a total of 227 preoperative serum samples from 193 OC patients and 34 patients with ovarian borderline tumours, and, in addition, serum samples from 86 healthy controls. An enzyme-linked immunosorbent assay (ELISA) was used to measure serum IgG antibodies against p53. The p53 protein used in the assay was produced as a hexahistidine-tagged fusion protein by baculovirus-infected Spodoptera frugiperda cells. Cut-off values for p53 AAb were evaluated, and correlations of p53 AAb with clinical-, biochemical data and survival were examined. We found a low sensitivity for p53 AAb alone, and no major additional effect of the detection rate of CA125 was found. No significant associations were found between p53 AAb and clinical stage, age, histological subtype and radicality after primary surgery. In contrast, we found significantly elevated CA125 levels in p53 AAb-positive patients compared to lower CA125 levels in p53 AAb-negative patients (p=0.003). No significant differences were found between p53 AAb-positive and p53 AAb-negative patients in the univariate and multivariate survival analyses. In conclusion, in a screening study for OC serum p53 AAb levels are of no diagnostic value, even if combined with the tumour marker CA125. The presence of increased serum p53 AAb in patients with diagnosed OC could not be correlated with any clinical data and preoperative serum p53 AAb status had no evident value.
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PMID:P53 autoantibodies in sera from Danish ovarian cancer patients and their correlation with clinical data and prognosis. 1239 Apr 12

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.
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PMID:Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer. 1456 28

Disruptions of the p53, retinoblastoma (Rb), and RAS signaling pathways and activation of human telomerase reverse transcriptase (hTERT) are common in human ovarian cancer; however, their precise role in ovarian cancer development is not clear. We thus introduced the catalytic subunit of hTERT, the SV40 early genomic region, and the oncogenic alleles of human HRAS or KRAS into human ovarian surface epithelial cells and examined the phenotype and gene expression profile of those cells. Disruption of p53 and Rb pathway by SV40 early genomic region and hTERT immortalized but did not transform the cells. Introduction of HRAS(V12) or KRAS(V12) into the immortalized cells, however, allowed them to form s.c. tumors after injection into immunocompromised mice. Peritoneal injection of the transformed cells produced undifferentiated carcinoma or malignant mixed Mullerian tumor and developed ascites; the tumor cells are focally positive for CA125 and mesothelin. Gene expression profile analysis of transformed cells revealed elevated expression of several cytokines, including interleukin (IL)-1beta, IL-6, and IL-8, that are up-regulated by the nuclear factor-kappaB pathway, which is known to contribute to the tumor growth of naturally ovarian cancer cells. Incubation with antibodies to IL-1beta or IL-8 led to apoptosis in the ras-transformed cells and ovarian cancer cells but not in immortalized cells that had not been transformed. Thus, the transformed human ovarian surface epithelial cells recapitulated many features of natural ovarian cancer including a subtype of ovarian cancer histology, formation of ascites, CA125 expression, and nuclear factor-kappaB-mediated cytokine activation. These cells provide a novel model system to study human ovarian cancer.
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PMID:A genetically defined model for human ovarian cancer. 1499 24

A case of mucinous cystadenoma of the testis in a 55-year-old man is reported. The tumor was confined to the testis and was clearly separated from the epididymis. There was no connection between the tumor cyst and the rete testis. The lumen of the cyst was lined with a single-layer of columnar cells interspersed with goblet cells. There was neither stromal invasion nor metastasis to other organs and there were no ovarian or germ cell neoplastic elements in the tumor. Immunohistochemical analysis revealed that MUC2, MUC5AC, carcinoembryonic antigen, CA19-9, CK7 and CK20 proteins were expressed on the tumor epithelial cells, whereas expression of MUC6, alpha-fetoprotein, CA125, human chorionic gonadotrophin, estrogen receptor, progesterone receptor, calretinin, chromogranin A, p53, cyclin D1 and bcl-2 proteins was absent. Ki-67 protein was weakly and sparsely expressed in the nuclei of epithelial cells. The mucinous cystadenoma in the present case, which was devoid of a connection to testicular appendices and had the immunohistochemical characteristics of gastrointestinal mucosa, might have originated from one-sided differentiation of teratoma cells.
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PMID:Immunohistochemical examination of mucinous cystadenoma of the testis. 1508 41

The aim of the study was to determine if biomarker expression could help discriminate between short-term and long-term survivors in women with advanced ovarian cancer. Fifty-one patients with stage III ovarian cancer were selected for the study, which included 28 short-term survivors (death from ovarian cancer within 18 months) and 23 long-term survivors (alive for more than 5 years). There was no difference between the two groups with respect to FIGO substage, age, World Health Organization score, and first-line platinum therapy. Classic clinical pathologic parameters were examined together with p53, Bcl-2, Ki-67, PDGFRalpha, P-glycoprotein, BRCA1, and DNA ploidy. Immunohistochemistry was used for scoring biomarker expression and image cytometry for DNA ploidy. All patients had primary debulking surgery followed by first-line platinum therapy. On multivariate analysis, the presence of ascites, debulking surgery and repeat laparotomy, clear-cell histology, elevated CA125, and high Ki-67 score were all found to be of prognostic importance. The long-term survivors were characterized by primary optimal cytoreduction surgery (<1 cm residual disease), attempt at maximal tumor debulking by experienced gynecological oncologic surgeons, and the absence of ascites. Normal CA125 level before platinum therapy and negative Ki-67 expression also predicted a more favorable prognosis.
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PMID:Prognostic factors in ovarian carcinoma stage III patients. Can biomarkers improve the prediction of short- and long-term survivors? 1634 77

Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of serum antibody of women with EOC or healthy controls to candidate TAA-coated microspheres was assayed in parallel. A Bayesian model/variable selection approach using Markov Chain Monte Carlo computations was applied to these data, and serum CA125 values, to determine the best predictive model. The selected model was subjected to area under the receiver-operator curve (AUC) analysis. The best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90] for discrimination between sera of EOC patients and healthy patients using antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model provided an AUC of 0.89 (95% CI, 0.84-0.92) compared with an AUC of 0.83 (95% CI, 0.81-0.85) using CA125 alone. However, using TAA responses alone, the model discriminated between independent sera of women with nonmalignant gynecologic conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71 (95% CI, 0.67-0.76) and 0.70 (95% CI, 0.48-0.75), respectively. Serum antibody to p53 and HOXB7 is positively associated with EOC, whereas NY-CO-8-specific antibody shows negative association. Bayesian modeling of these TAA-specific serum antibody responses exhibits similar discrimination of patients with early-stage and advanced-stage EOC from women with nonmalignant gynecologic conditions and may be complementary to CA125.
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PMID:Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection. 1645 40


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