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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 gene is located on the short arm of chromosome 17. It encodes a 53-kd nuclear protein (p53) found in scant amounts in normal tissue. Mutations of the p53 gene have been reported in different human tumours. In breast cancer, it has been noted that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, although there is a high degree of variability, which may be due to different immunohistochemical techniques, varying assessment of results and the type of monoclonal antibody used. This study is an immunohistochemical analysis of p53 expression in 192 cases of infiltrating ductal carcinoma of the breast, correlating it with clinicopathological factors and the clinical course of the disease. Of all the breast-cancer tissue analysed, stains for p53 antibody were found in 87 tumours (45.3%). The results of multivariate analysis show that the independent predictors related to recurrence are tumour size, lymph-node metastasis and p53, while those related to death are necrosis, lymph-node metastasis and p53. In summary, our series showed prognostic significance between the expression of p53 and shorter survival time and disease-free interval for all patients in general as well as those who presented lymph-node metastases at the time of diagnosis.
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PMID:Prognostic value of p53 protein expression and clinicopathological factors in infiltrating ductal carcinoma of the breast. A study of 192 patients. 1119 17

The main reason for the recent interest in p53 is that almost 50% of human cancers contain p53 gene mutations. The majority of studies on p53 alterations in breast cancer have been limited to the isolated cases of ductal carcinoma in situ and infiltrating ductal carcinoma. The aims of this study were to determine the status and timing of p53 mutation in the progression from atypical ductal hyperplasia to invasive cancer, and to evaluate the patterns of p53 mutations in noninvasive and invasive lesions. Available lesions of invasive (n=88) and noninvasive (n=76) lesions were microdissected in 107 paraffin-embedded tissues (19 ductal carcinomas in situ, 57 invasive carcinomas with intraductal components, and 31 pure invasive carcinomas) and double-strand DNA sequencing was performed in exon 4-9 of the p53 gene. Among in situ cancers without invasive disease 36.8% had p53 mutations whereas in situ cancer with concurrent invasive disease showed p53 mutations in 33.3% of cases. In particular, two of seven atypical ductal hyperplasias harbored p53 alterations (one insertion and one missense mutation) in exon 8. The invasive component harbored p53 mutations in 30 of 88 cases (34.1%). We also discovered a novel deletion of 14 bp in exon 6 of two invasive lesions. The invasive component (1.33+/-0.13) carried a greater number of p53 mutations than its counterparts (1.19+/-0.10) and demonstrated more frequent multiple mutations (23.3% vs. 15.4%), but without statistical significance. Moreover, no statistical significance could be attached to the mutation frequency in the zinc-binding domains (26.7% vs. 15.4%), the directly DNA contact region (13.3% vs. 15.4%) and the missense mutation of p53 (50.0% vs. 57.7%) of the two groups. Based on our results, in spite of the small number of the lesions investigated, p53 mutation can occur at the stage of atypical ductal hyperplasia. The hypermutability and the specific p53 mutations involving the biologically functional domain (e.g., zinc binding domain or DNA contact region) have an insignificant influence on invasive progression in the breast cancer.
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PMID:The timing and characterization of p53 mutations in progression from atypical ductal hyperplasia to invasive lesions in the breast cancer. 1171 68

Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified which includes p53. Alterations of p53 are one of the most common abnormalities detected in primary breast cancer. In this study alteration of p53 in primary carcinoma breast was correlated with other pathological variables and disease outcome. In this prospective study the expression of p53 oncoprotein was analyzed immunohistochemically on 315 patient's tumour specimens of infiltrating ductal carcinoma of breast from 1992 to 1997. These patients also had axillary lymph nodes sampling. Both univariate and multivariate statistical analysis was performed to analyze results including disease outcome. Overexpression of p53 was observed in 55.23% tumours. Axillary lymph node metastasis had significant correlation with positivity of p53 (p<0.05). A significant number of p53 patients developed local recurrence and distant metastases to brain, liver, lung and bone (p< 0.05). At a median follow-up of 48 months (4 years) in p53 positive patients, the median overall survival (OS) was 3.0 years and disease free survival (DFS) was 2.5 years. p53 negative tumour patients showed a better survival. In this group the median OS was 3.8 years and the DFS was 3.3 years. The above findings have reinforced the view that p53 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.
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PMID:Relationship of p53 expression with clinicopathological variables and disease outcome: a prospective study on 315 consecutive breast carcinoma patients. 1216 94

Identification of myoepithelial cells using antibodies to cytoskeletal proteins, such as smooth muscle myosin heavy chain (SMM-HC) and calponin, can play an important role in distinguishing invasive carcinoma from its histologic mimics. However, antibodies to these proteins may also cross-react with stromal myofibroblasts and vascular smooth muscle cells. It has recently been demonstrated that myoepithelial cells express the nuclear protein, p63, a member of the p53 gene family. We compared the patterns of reactivity of antibodies with p63, calponin, and SMM-HC on 85 breast lesions, including 11 cases of sclerosing adenosis, 33 cases of ductal carcinoma in situ, including 10 that showed microinvasion, 6 cases of lobular carcinoma in situ, and 35 cases of infiltrating ductal carcinoma. All three antibodies were positive on the vast majority of myoepithelial cells in all cases. A small minority of cases showed focal gaps in the revealed myoepithelial cell layer, reflected in discontinuous positive immunostaining around noninvasive epithelial nests (including ductal carcinoma in situ). No case showed p63 expression by myofibroblasts or vascular smooth muscle cells, whereas myofibroblasts expressed, in 8% and 76% of cases, SMM-HC and calponin, respectively. Although no tumor cell reactivity was noted with antibodies to calponin or SMM-HC, tumor cells in 11% of cases showed at least focal p63 expression. And although antibodies to p63 offer excellent sensitivity and increased specificity for myoepithelial detection relative to antibodies to calponin and SMM-HC, they have the following diagnostic limitations: 1) they occasionally demonstrate an apparently discontinuous myoepithelial layer, particularly around ductal carcinoma in situ, and 2) they react with a small but significant subset of breast carcinoma tumor cells. p63 may represent a myoepithelial marker that can complement or replace SMM-HC and/or calponin in the analysis of difficult breast lesions.
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PMID:Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain. 1250 30

We report a 54-year-old woman with Cowden's disease (CD) who was found to carry a novel germline mutation in the PTEN gene. The mutation (c.334C-->G) introduced a splice donor site within exon 5 that caused the expression of an aberrant transcript lacking 159 nucleotides corresponding to codons 112-164. Clinically, the patient showed multiple benign hamartomatous lesions of the skin, papillomatosis of the lips and oral mucosa, polyposis coli and bilateral fibrocystic disease of the breast. In addition, she developed different types of malignant neoplasms, including bilateral carcinomas of the breast and malignant melanomas of the skin. Molecular genetic analysis of a benign skin hamartoma and an invasive ductal breast carcinoma revealed loss of heterozygosity (LOH) at microsatellite markers on chromosome 10 in the carcinoma but not in the hamartoma. The breast carcinoma additionally carried a somatic TP53 point mutation (c.466C-->G; R156G) that was associated with LOH on 17p and nuclear p53 protein accumulation. Taken together, our findings indicate that benign hamartomas in CD may develop without loss of the second (wild-type) PTEN allele, whereas the pathogenesis of malignant tumours, such as breast carcinomas, appears to require the complete inactivation of Pten as well as further alterations such as the loss of p53-dependent growth control.
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PMID:Cowden's disease: clinical and molecular genetic findings in a patient with a novel PTEN germline mutation. 1278 40

The role of p53 as a prognostic factor is not clear. P53 named as "guardian of the genome" plays an important role in many intracellular regulatory systems, one of which is apoptosis, having an impact on tumor kinetics. A retrospective study was undertaken to assess the relationship of the Nothingham Prognostic Index (NPI) to p53 expression and apoptotic cell counts. To conduct the study, 160 successive cases of infiltrating ductal carcinoma of the breast were included. P53 was assessed on AP-AAP stained sections. Apoptotic cell counting (ACC) was done on the HE stained routine sections in 10 HPFs. Clinical data were derived from the hospital files. Apoptotic cell counts were higher in the p53 positive group but the difference was not significant (p=0.079). P53 positivity was found to be related to the disease-free survival (DFS) (p=0.008). NPI was significantly higher in apoptotic cell containing group (p=0.006). There was a positive linear correlation between ACC and NPI scores (p=0.004). This correlation was not present between apoptosis and disease free survival. P53 expression was found to be related with DFS but not with the NPI which is a score composed of the best prognostic indicators known today. In contrast to this, ACC was found to be closely and linearly associated to the known prognostic factors. This may suggest that the apoptotic cell counts done on routine sections may be used as a part of prognosis assessment in infiltrating ductal carcinoma.
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PMID:Is Nothingham Prognostic Index correlated with apoptosis and p53 expression in infiltrating ductal carcinoma of the breast? 1285 14

The aim of this study was to determine the chemosensitivity of infiltrating lobular breast carcinoma (ILC) in comparison with infiltrating ductal carcinoma (IDC). Between 1987 and 1995, 457 patients with invasive T2>3 cm-T4 breast carcinomas were treated with primary chemotherapy (CT), surgery, radiation therapy. Clinical response, the possibility of breast preservation, pathological response and survival were evaluated according to the histological type. In order to evaluate the biological differences between ILC and IDC patients and their implication with regard to tumour chemosensitivity, additional immunohistochemical stainings (oestrogen receptor (ER), Bcl2, p53, c-erbB-2 and Ki67) were performed on 129 pretherapeutical specimens. 38 (8.3%) ILC were diagnosed by core needle biopsy before CT. ILC was an independent predictor of a poor clinical response (P=0.02) and ineligibility for breast-conserving surgery after neoadjuvant chemotherapy (P=0.03). Histological and biological factors predicting a poor response to CT (histological grade, ER, Ki67 and p53 status) were more frequent in ILC than in IDC patients. After a median follow-up of 98 months (range: 3-166), the low chemosensitivity of ILC did not result in a survival disadvantage. Our results demonstrate that ILC achieved a lower response to CT than IDC because of their immunohistochemical profile. Preoperative CT did not allow a high rate of conservative treatment for ILC and therefore the use of neoadjuvant CT for ILC patients should be questioned.
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PMID:The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. 1474 51

Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p<0.05) was demonstrated between monosomy 1 and patients' age below 50 years, and between monosomy 1 and poor survival, respectively. Disomy 8 was significantly associated with P53 expression. A borderline significant correlation was demonstrated between polysomy 8 and diploid DNA content, as well as between disomy 1 and disease-free status of the patients. Chromosome 1 and 8 copy numbers may be considered as useful prognostic markers in invasive ductal carcinoma of the breast.
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PMID:Prognostic value of chromosome 1 and 8 copy number in invasive ductal breast carcinoma among Iranian women: an interphase FISH analysis. 1619 69

The HER-2/neu gene is a proto-oncogene that is amplified in 10-30% of breast cancers. New drugs for targeted therapy, such as Herceptin, are effective for patients with HER-2/neu-positive tumors, making it necessary to have a noncostly and accurate method to assess HER-2/neu status. We studied the correlation of findings made by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) staining and the possibility of combining IHC and other clinicopathologic characteristics of breast tumors to predict FISH-determined HER-2/neu status. The clinicopathologic characteristics analyzed were the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A total of 199 cases of invasive breast cancer studied at the UCLA Pathology Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+, and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of the respective groups. Our study showed a strong association between the FISH-negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be necessary in these cases (p<0.0001). Although the concordance between IHC 3+ and FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail to show gene amplification by FISH. HER-2/neu positivity was found to be proportionally associated with increasing grade in infiltrating ductal carcinoma (p<0.0001). p53-positive tumors are more likely to be HER-2/neu amplified (p=0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu positivity by FISH (31.15%, p=0.0016). FISH-determined HER-2/neu status is not associated with histologic type, tumor size, nodal status, lymph-vascular invasion, or patient age.
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PMID:Histopathologic characteristics predicting HER-2/neu amplification in breast cancer. 1629 88

This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.
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PMID:Correlations in survivin expression with the expression of p53 and bcl-2 in invasive ductal carcinoma of the breast. 1804 10


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