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)

Ovarian granulosa cell tumors (GCTs) behave unpredictably. Stage I patients suffer recurrences many years after treatment, and histopathologic evaluation of the primary GCT offers only a few clues. Grading, in particular, is largely ineffective. Ki67 (MIB-1) and p53 monoclonal antibodies (active on paraffin embedded tissues) provide insight into nuclear proliferation and control, respectively. In this study, the authors hypothesized that these molecular markers will help predict the clinical behavior of GCTs. Paraffin sections from 68 GCTs (arising in 56 patients: 53 primary and 15 recurrent) including 34 typical and 27 diffuse adult, and seven juvenile types were immunostained for Ki67 (MIB-1 clone; Immunotech, Westbrook, ME) and p53 (DO7 clone; Novacastra Laboratories, UK). The Ki67 proliferation index (Ki67PI = percentage immunoreactive on a count of at least 400 nuclei) ranges from 1 to 50% (mean, = 12.2%; median, 9.3%). Nineteen percent of GCTs exhibited focal p53 immunoreactivity; the number of GCTs and proportion of nuclei decorated were as follows: four, <1%; seven, 1% to 10%; and one, 20%. Ki67PI was higher in recurrent tumors (P<.001) and correlated with mitotic rate (r = .75; P<.0001). p53 staining was associated with juvenile type GCTs (P<.001) and higher Ki67PI (P<.005). Other histopathologic features exhibited no association with p53 staining or Ki67PI. Follow-up was available for 54 of 56 patients: 18 suffered recurrences after 16 to 229 months (mean, 72.1 months; median 59 months), and 36 were disease free 16 to 369 months (mean, 78.2 months; median, 70 months) after diagnosis. Curiously, high Ki67PI and mitotic rates of primary GCT correlated weakly with a disease-free course (P=.03 and .07 respectively). Disease recurrence was associated with stage >I (P<.0005), vessel invasion in the capsule (P<.001), ruptured tumors (P<.005), and older patients (P<.02). p53 staining and size or subtype of GCT exhibited no prognostic value. For 12 patients, paired primary and first recurrence of GCT showed a striking increase in Ki67PI (P<.00005) and mitotic activity (P<.02) in the recurrence. p53 expression also appeared (de novo) in two recurrent GCTs. The interpretation of focal p53 staining (>10% nuclei decorated in only one GCT) is controversial. Some investigators suggest that this represents overexpression of wild type p53 rather than p53 gene mutation. Primary GCTs exhibit a wide spectrum of proliferative activity, and the seven juvenile GCTs (the most proliferative type) demonstrated no recurrences in this study. Recurrent GCTs displayed a transformation of molecular markers to increased proliferative activity and overexpression of p53, fundamentally, by these markers, a different GCT than the primary one. These findings suggest a molecular basis for the lack of histopathologic predictors for recurrence. Factors other than proliferation of the primary GCT (which relates most closely to grading) either extrinsic to the neoplasm (host dependent) or as yet undetectable must determine malignant behavior.
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PMID:Transformation in recurrent ovarian granulosa cell tumors: Ki67 (MIB-1) and p53 immunohistochemistry demonstrates a possible molecular basis for the poor histopathologic prediction of clinical behavior. 860 43

Alterations in the tumor-suppressor gene p53 are common in many types of human malignancies, but the potential role of p53 in the pathogenesis of cutaneous melanoma is controversial. The gene product, p53 protein, is normally present in very small amounts in noncancerous tissues. Missense mutations lead to accumulation of mutant p53 in the cells, which makes it detectable immunohistochemically in many cancers. Formalin-fixed, paraffin-embedded sections of 14 primary invasive melanomas, 3 cutaneous melanoma metastases, and 10 predominantly intradermal melanocytic nevi were reacted with a panel of three anti-p53 monoclonal antibodies (mAbs) (PAb240, PAb1801, and DO7) and a mAb against Ki-67 (MIB-1), a marker of cellular proliferation. p53 was not detected in morphologically normal epidermal melanocytes or nevus cells. A single primary invasive melanoma, having a very high index of proliferation (Ki-67 expression in > 50% of cells), had diffuse nuclear labeling with all three anti-p53 mAbs used. Abnormalities of p53 expression occur rarely in cutaneous melanomas, but overexpression of p53 may occur in a subset of melanomas with a high index of proliferation.
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PMID:p53 expression is rare in cutaneous melanomas. 860 Jul 97

There is still controversy over the criteria for malignancy of smooth muscle tumors (SMTs) of the uterus. We examined 51 cellular SMTs using immunohistochemistry for MIB-1, proliferating cell nuclear antigen (PCNA), p53, HHF35, alpha-smooth muscle actin (SMA), and flow cytometry. Morphologically, the 51 cases were classified into 24 leiomyosarcomas (LMS), two uncertain malignant potential, four bizarre leiomyomas, and 21 cellular leiomyomas. The mean values of the MIB-1 and PCNA indices showed significant differences between LMS and benign SMTs. p53 cells were positive in eight of 24 leiomyosarcomas, and 12 of 22 were aneuploid. HHF35 and alpha-SMA showed a diffuse positivity in almost all the benign SMTs. In contrast, 10 of the 24 LMS were either focally positive or negative for SMA. Using a logistic regression model, at cut-off points of 3.6 on the MIB-1 index and 15.6 on the PCNA index, the LMS and the benign SMTs were classified with an overall accuracy of 92% and 82%, respectively. Moreover, by combining the MIB-1 index and alpha-SMA positivity, the cut-off point could be established at 0.492 on the probability scale with the highest overall accuracy of 96%. Regarding the prognosis of LMS, p53 positivity was correlated with survival (p = 0.0357). A combination of the MIB-1 index and alpha-SMA was helpful in distinguishing between LMS and benign SMT. Moreover, p53 positivity was considered to be a good marker for predicting the prognosis of LMS.
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PMID:Leiomyosarcoma versus bizarre and cellular leiomyomas of the uterus: a comparative study based on the MIB-1 and proliferating cell nuclear antigen indices, p53 expression, DNA flow cytometry, and muscle specific actins. 860 25

The prognostic significance of p53 gene abnormalities was investigated in 919 primary breast-cancer patients. p53 expression and tumour-cell proliferation fraction determined by MIB-1 count, p53 exon 5 and 6 mutations and HER-2/neu oncogene amplification were detected by immunohistochemistry, PCR-SSCP and slot-blot hybridization, respectively. Increased MIB-1 count, p53 expression, HER-2/neu oncogene amplification and p53 mutations were detected in 33%, 29%, 10% and 8% of tumours, respectively. Statistically significant associations were observed between p53 expression or MIB-1 count and age below 50 years, high-grade tumours, medullary carcinomas, and absence of hormone receptors. p53 mutations were associated with increased MIB-1 count, HER-2/neu oncogene amplification and absence of hormone receptors, but not with age, tumour size or grade, histological subtype, or the number of axillary nodes involved. After a median follow-up of 66 months, p53 expression was observed to be associated with significant increases in risk of both relapse and death from breast cancer, but not after adjusting for the effect of other parameters. In these analyses, MIB-1 count, and not HER-2/neu oncogene amplification, was an independent predictor of prognosis. In node-negative patients, only p53 exon 5 and 6 mutations and MIB-1 count were associated with a statistically significant increase in risk of death from breast cancer, independent of tumour size and ER concentration. We conclude that tumour-cell proliferation fraction, as measured by MIB-1 count, is the most useful parameter of breast-cancer prognosis, with the exception of ER, tumour size and the number of axillary nodes involved.
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PMID:Relationship between p53 gene abnormalities and other tumour characteristics in breast-cancer prognosis. 860 82

Chordoma shows various degrees of atypia histologically, however, the relationship between the histological features and the biological behavior still remains controversial. The authors subclassified 17 specimens with chordoma into two groups (ie, trabecular type showing a trabecular patterns and solid type mainly consisting of a diffuse proliferation of tumor cells). The histological grading was performed according to the degree of nuclear atypia on a scale of 1 to 3. Using DNA flow cytometric and immunohistochemical techniques, both the proliferative index (% S + G2 + M phase) and the MIB-1 labeling index (LI) of the tumor cells were estimated regarding their proliferative activities. In addition, p53 overexpression was also investigated using immunohistochemical techniques. There were eight (47.1%) specimens of trabecular type and nine (52.9%) of solid type. In nine specimens of solid type, those with higher nuclear atypia (grade 2 or 3) were significantly more frequent (five specimens, 55.6%) than in trabecular type in which all of the eight specimens were grade 1 (P = 0.44). The proliferative index was significantly higher in grade 2 or 3 lesions than in grade 1 lesions (P = .014), and the MIB-1 LI tended to be higher in solid type than in trabecular (P = .088). p53 overexpression was detected in two specimens of solid type, and the MIB-1 LI in these two specimens was significantly higher (P = .037) than that in the specimens without p53 overexpression. It was considered that the preceding anaplastic histological features, including either diffuse proliferation or high grade nuclear atypia, together with p53 overexpression, were thus closely related to the proliferative activities in chordomas.
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PMID:Proliferative activities in conventional chordoma: a clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia. 861 82

DNA flow cytometry and the monoclonal antibody DO7 were applied in formalin-fixed, paraffin-embedded specimens from 34 primary male breast carcinomas to verify whether DNA ploidy and p53 expression were associated with survival and proliferative activity. They were compared with tumor clinicopathologic features, sex steroid hormone receptors and cell proliferative activity, assessed by the counts of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody PC10 against the proliferating cell nuclear antigen and the monoclonal antibody MIB-1. A significant correlation was found between survival and tumor ploidy (median survival, 77 months for diploid but only 38 months for aneuploid cases; P = .03) and p53 expression (median survival, 95 months for cases with p53 scores < or = 14.06% versus 33 for cases with P53 scores > 14.06%; P = .0004; median survival, 99 months for p53 negative vs 39 for positive cases; P = .007). Tumor histological grade (P = .006), AgNOR counts (P = .0001), PC10 scores (P = .002), and MIB-1 scores (P = .001) were also associated with prognosis. In the multivariate analysis, only p53 scores (P = .001) or p53 immunopositivity (P = .003) and AgNOR counts (P = .022) retained an independent prognostic significance. Aneuploid tumors had higher AgNOR counts (P = .002), PC10 (P = .007), MIB-1 (P = .006), and p53 scores (P = .01) than diploid cases. A linear relationship was observed between p53 scores and AgNOR counts (r = .41; P = .014), PC10 (r = .46; P = .005), and MIB-1 scores (r = .44; P = .011). These results indicate that DNA ploidy and p53 expression are associated with survival and cell proliferative activity in male breast carcinoma. Quantitative parameters, such as DNA ploidy, p53 scores, AgNOR counts, PC10, and MIB-1 scores substantially improve the prognostic significance of the traditional parameters in male breast carcinoma.
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PMID:DNA ploidy and p53 expression correlate with survival and cell proliferative activity in male breast carcinoma. 869 11

Primary cerebral lymphomas (PCL's) are rare tumors which, however, occur with increasing frequency. The present study investigated 55 PCL's of B-cell type, 36 in immunocompetent and 19 in AIDS-patients and 6 cases of intravascular lymphomatosis. In immunocompetent patients, proliferative indices as evaluated by PC10 and MIB1 reflected the histologic grade. Low grade tumors had a mean PCNA and MIB-1 count of 19 and 18.8 (SD 14.7 and 13.2), respectively, and high grade neoplasias showed counts of 56.7 and 47.1 (SD 19 and 17.4), respectively. No correlation of both indices with patient survival was found. 21 cases (58.3%) displayed p53-positivity of varying degree and 19 cases (52.7%) harbored bcl-2 positive neoplastic cells. Immunocompetent cases were always negative for Epstein-Barr virus RNA and lmp-1-protein. In AIDS-cases, 13 cases (68.4%) showed up lmp-1 positivity and 15 cases (78.9%) had EBER-RNA. bcl-2 positive cells were detected in 5 cases (26.3%) and all cases were p53-negative. These results are in keeping with a role of EBV in the pathogenesis of primary cerebral lymphomas in AIDS-, but not in immunocompetent patients. None of the cases with intravascular lymphomatosis showed an expression of bcl-2 or p53 oncoproteins or lmp-1 and none had EBER-RNA.
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PMID:Primary non-Hodgkin lymphomas of the CNS-proliferation, oncoproteins and Epstein-Barr-virus. 870 88

The clinical significance of vimentin intermediate filament (VIF) expression was studied in relation to other established prognostic parameters in primary breast cancer. Archival tumour samples embedded in paraffin were examined by immuno-histochemistry with monoclonal antibodies (MAbs) to VIF, p53 protein and cell proliferation marker MIB-I. The vimentin staining pattern was heterogeneous, but in vimentin-positive areas > 80% of the tumour cells were positive. There was no association between vimentin expression and tumour size or the number of axillary lymph nodes involved. Vimentin expression was significantly associated with high-grade tumours, absence of hormone receptors, increased p53 expression and high tumour proliferation fraction as estimated by MIB-I count. Despite these associations with several recognised features of tumour aggressiveness, vimentin expression was not associated with increase in risk of relapse or death from breast cancer.
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PMID:Vimentin expression is not associated with poor prognosis in breast cancer. 870 8

Expression of bcl-2 is most commonly associated with the t(14;18) translocation present in most folicular lymphomas (1). More recently, bcl-2 oncoprotein has been identified in normal tissues and in nonhematologic malignancies. In this study, we investigate the use of bcl-2 as a marker to distinguish metastatic breast carcinoma from primary lung and gastric cancers, and we evaluate the role of bcl-2 as an independent prognostic factor in breast carcinoma and its relationship to other breast cancer markers. bcl-2 immunostains were done on 371 adenocarcinomas of the breast, lung, and stomach. Additionally, 231 samples of metastases from patients with breast or gastric cancer were evaluated for bcl-2 expression. All breast cancer tissue samples had immunohistochemical data on expression of estrogen and progesterone receptors, p53, neu/cerb2, and MIB-1. A large proportion (79.3%) of invasive breast carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary and gastric carcinomas did. Moreover, staining was moderate to intense in 70.2% of the breast cancers, compared with only one specimen of lung carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate staining. There was agreement of bcl-2 expression between primary and metastatic sites in all specimens except one. Expression of bcl-2 in breast adenocarcinomas was significantly associated with hormone receptor positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-positive specimens were estrogen receptor negative and 24.2% of bcl-2-positive specimens were progesterone receptor negative. Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer. We conclude that adenocarcinomas with intense bcl-2 staining are more likely to be of breast than of pulmonary or gastric origin. We recommend the addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP-15, and S100) that might contribute to the identification of a larger proportion of metastatic breast carcinomas, because almost one-half of the estrogen-receptor negative cancers were bcl-2 positive.
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PMID:Expression of bcl-2 by breast cancer: a possible diagnostic application. 872 86

We investigated the relationship between immunohistochemical estimates of proliferative activity and expression of bcl-2 protein and mutant p53 protein in 23 cases of soft tissue sarcoma. Furthermore, the reproducibility of estimates of proliferative activity was analysed and correlations between the variables and with mitotic score were investigated. Proliferative activity was assessed by use of monoclonal antibody MIB-1 and staining for iododeoxyuridine (IdUrd), and evaluated in multiple, random, systematically sampled fields of vision. MIB-1 indices were higher than those of IdUrd but for each case the two values were positively correlated (r = 0.78). The MIB-1 index correlated positively with mitotic score (2P < 0.001) and malignancy grade (2P = 0.001). The intraobserver reproducibility of the MIB-1 and IdUrd indices were excellent (r = 0.98 and r = 0.90, respectively). p53 expression was detected in 43% and strong bcl-2 expression was present in 57% of the studied cases. Expression of p53 and bcl-2 were not significantly correlated to proliferative activity or the histological features. We conclude, that the MIB-1 index is a reliable and reproducible estimate of proliferative activity and might improve the accuracy of conventional malignancy grading of soft tissue sarcomas. Furthermore, the results indicate that neither mutant p53 protein nor bcl-2 oncogene alone are sufficient to induce increased proliferation in these sarcomas.
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PMID:MIB-1 expression and iododeoxyuridine labelling in soft tissue sarcomas: an immunohistochemical study including correlations with p53, bcl-2 and histological characteristics. 873 19


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