Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Salivary duct carcinoma (SDC) was first described by Kleinsesser in 1968 and was classified as an independent entity by the 1991 Revised World Health Organization. It is a rare but highly malignant tumor. We reviewed pathology in 49 cases of salivary adenocarcinoma, and diagnosed 6 cases as SDC. All had a rapidly enlarged mass in the parotid gland. All were men, and 4 involved facial palsy and metastasis to cervical lymph nodes. Fine needle aspiration biopsy was conducted in 3 cases, but none was diagnosed as SDC. Two had chemotherapy, but showed no effect. All underwent surgery, but only 1 survived more than 4 years. Immunohistochemically, none showed s-100 protein. Four showed PCNA and p53 protein. Highly positive cells of PCNA and p53 were found around comedo necrosis.
 ...
PMID:[Clinicopathological study of salivary duct carcinoma]. 1213

In the multistep progressive pathogenesis of human breast cancer, comedo ductal carcinoma in situ (DCIS) represents a preinvasive precursor lesion for therapy resistant invasive cancer. Human tissue derived cell culture models exhibiting molecular similarities to clinical DCIS facilitate an important preclinical mechanistic approach for evaluation of preventive efficacy of natural and synthetic chemopreventive compounds. Natural phytochemicals present in fresh fruits, vegetables and grain products are likely to offer protection against cancer. The clinical efficacy of these natural phytochemicals, however, depends on extrapolation, and is therefore equivocal. The present study determined whether the natural soy isoflavone genistein (GEN) inhibited aberrant proliferation in 184-B5/HER cells (a model for human comedo DCIS) and identified possible mechanisms responsible for its efficacy. Human reduction mammoplasty derived HER-2/neu oncogene expressing preneoplastic 184-B5/HER cells represented the experimental system. Flow cytometry and cellular epifluorescence based assays were utilized to quantitate the alterations in cell cycle progression, cellular apoptosis, and in the status of cell cycle regulatory and apoptosis-associated gene product expression. The 184-B5/HER cells exhibited specific immunofluorescence to p185HER, p53, EGFR, but not to ERalpha, thus resembling comedo DCIS. Treatment of 184-B5/HER cells with GEN resulted in a dose-dependent decrease in the viable cell population, increase in the G0/G1:S + G2/M ratio and enhancement of sub G0/G1 (apoptotic population). Exposure to the maximum cytostatic 10 microM dose of GEN down-regulated HER-2/neu mediated signal transduction as evidenced by a 73.9% decrease (p=0.001) in p185HER specific, and a 89.8% decrease (p=0.001) in phosphotyrosine specific immunofluorescence. The increase in G0/G1:S + G2/M ratio in response to the treatment with 10 microM GEN was associated with a 85.5% decrease (p=0.001) in immunoreactivity to PCNA and a 128.6% increase (p=0.004) in immunoreactivity to the cyclin dependent kinase inhibitor p16INK4. The induction of apoptosis by GEN was associated with a 52.8% decrease (p=0.001) in the immunoreactivity to antiapoptotic Bcl-2 and with a 195.9% (p=0.001) increase in the immunoreactivity to proapoptotic Bax. Thus, preventive efficacy of GEN in HER-2/neu+/ER- 184-B5/HER cells may be due to its ability to down-regulate HER-2/neu mediated signal transduction, increase the expression of the cyclin dependent kinase inhibitor p16INK4, and induce Bcl-2 dependent apoptosis. These data provide evidence that GEN may be a potential chemopreventive lead compound for human comedo DCIS. The 184-B5/HER cells, may therefore, provide a high throughput mechanistic bioassay to identify new chemopreventive agents for human breast cancer.
 ...
PMID:Soy isoflavone genistein modulates cell cycle progression and induces apoptosis in HER-2/neu oncogene expressing human breast epithelial cells. 1223 20

The breast cancer has become more frequent with women lately. The reasons for that are longer life, effects of external factors and hormone effects, estrogen in particular either natural or synthetic. Today's trend is to detect these tumors in situ in early stage where two types of lesions are distinguished: ductal carcinoma in situ (DCIS) and lobular carcinoma in situ. It is important to determine by means of histochemistry receptors for estrogen, progesteronee, C-erb B-2, p53 and profilic nucleic antigen (PCNA) in tissue of these tumors not only for prognostic importance, bat for selection of the optimal treatment method. The aim of the study is to analyze the frequency of the said receptors in 22 samples of tissue "ex tempore" where DCIS was found. Out of 50 cases where areas of micro-calcification identified on mammograms, 22 cases were separated with DCIS "ex tempore". Applying the immunohistochemistry method with commercial antibodies produced by the firm "Dako" receptors of estrogen, progesterone, C-erb B-2, p53 and PCNA were identified. Receptors were identified by monoclonal antibodies according to the instruction supplied by the firm. Regarding the type of DCIS the finding was 18% solid, 4.5% comedo, 4.5% parietal, 13.6 cribriform, while mixed types were found in 59.1% cases. Out of 22 women with DCIS, 4 of them or 18.2% had positive P-53; 13 or 59.1% PCNA, 15 or 68.2% positive C-erb B-2, 8 or 36.4% positive estrogen, 4 or 18.2% positive progesterone receptors. When the sample is submitted for patho-histologic testing it is necessary to determine the subtypes of DCIS, number of ducts affected by subtypes, other accompanying profilic changes and it is compulsory to identify receptors for C-erb B-2, estrogen and progesteronee, which can be done in any patho-histologic lab. The benefit of their identification before passing a decision about the therapy is big, i.e. they determine the type of therapy which has a preventive effect on the rest od tissue both affected and sound breast.
 ...
PMID:[Markers of ductal carcinoma in situ]. 1237 62

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.
 ...
PMID:Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases. 1282 6

Breast carcinoma is usually accompanied by an invasive component with an intraductal component, and each component shows different morphological features. We evaluated whether the presence or absence of comedonecrosis is correlated with prognosis and biological features in node-negative invasive breast carcinoma. Ninety-four node-negative breast carcinomas with an intraductal component were classified into two types: comedo type (n = 36) showing comedonecrosis partly or extensively in the intraductal component, and non-comedo type (n = 58) showing either an absence or small foci of necrosis. The Kaplan-Meier method was used to calculate disease-free survival. Immunohistochemical examination for p53 and HER-2 was conducted on the comedo (n = 35) and non-comedo (n = 47) type tumor specimens. Disease-free survival was significantly shorter in the comedo type than in the non-comedo type (P = 0.019). The expression of p53 was observed in 16 (45.7%) of the 35 comedo type cases, but only in two (4.3%) of the 47 non-comedo type cases (P < 0.0001). HER-2 overexpression was observed in seven (20.0%) of the 35 comedo type cases, while none of the 47 non-comedo type cases overexpressed HER-2 (P < 0.0001). These results suggest that the presence of comedonecrosis may be predictive of an unfavorable prognosis with aggressive biological behavior in node-negative invasive breast carcinoma.
 ...
PMID:Comedonecrosis is an unfavorable marker in node-negative invasive breast carcinoma. 1289 28

We studied 10 cases of primary pure testicular neuroendocrine carcinoma. Patients were between 16 and 48 years old and had testicular swelling with pain or a painless testicular mass and no history of neuroendocrine carcinoma or other malignant neoplasm. All underwent orchiectomy. The tumors were low (n = 9) and intermediate (n = 1) grades with a variegated histologic appearance characterized by a nesting pattern, cords of neoplastic cells with rosettes, or sheets of neoplastic cells. Mitotic activity was lacking in 9 cases. In 1 case, mitotic figures ranged from 7 to 8 per 10 high-power fields, and cellular atypia and comedo-like necrosis were present. Immunohistochemical studies using a keratin cocktail, chromogranin, synaptophysin, epidermal growth factor, p53, placental-like alkaline phosphatase, and CD117 (c-kit) were performed in all cases. Keratin, chromogranin, and synaptophysin were positive in all tumors. Clinical follow-up information was obtained for 6 patients (range, 12-60 months): 5 with low-grade tumors were alive 24 to 60 months after diagnosis; 1 with an intermediate-grade tumor died of tumor 12 months after initial diagnosis. The behavior of these tumors, while in the testicular region, correlates well with the histologic grade. We propose replacing the term testicular carcinoid with neuroendocrine carcinoma, which better reflects the nature of these neoplasms.
 ...
PMID:Neuroendocrine carcinomas (carcinoid tumor) of the testis. A clinicopathologic and immunohistochemical study of ten cases. 1498 45

Basaloid squamous carcinoma (BSC) is a rare variant of squamous cell carcinoma (SCC). In this study, clinicopathological and immunohistochemical characteristics of 12 superficial esophageal BSCs were examined and compared with those of typical superficial SCCs. Eight cases were classified into an elevated type, and the other four into a depressed type. High-grade intraepithelial neoplasia was not observed around the invasive lesions in five cases, and only BSC components were apparent. High-grade intraepithelial neoplasia was demonstrated in seven cases, five of which had both BSC and SCC components in the invasive lesion. A cribriform growth pattern, comedo-type necrosis, and hyaline deposits were conspicuous histological findings. CK14 was positively stained in 90% of the series, but the proportion of positive cells was small in most cases. Type IV collagen was increased or well preserved in the basement membrane in 70% of cases, but heparan sulfate was decreased in the majority. In comparison with SCCs, lymphatic permeation was observed less frequently. However, regarding the frequencies of venous permeation, nodal metastasis, p53 protein expression, and Ki-67 labeling index, no significant differences were noted. Thus, esophageal BSCs demonstrate the pathological features characteristic of an early stage, but pathological parameters related to biological behavior do not significantly vary from those typical of SCCs.
 ...
PMID:Superficial basaloid squamous carcinoma of the esophagus. A clinicopathological and immunohistochemical study of 12 cases. 1470 37

Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined. Hematoxylin- and eosin-stained sections of all the cases were studied for several morphological parameters and their immunophenotype profile. These findings were correlated with patient and tumor characteristics and survival data. ER-negative tumors constituted 30% of the primary operable breast cancer series. The majority of tumors were grade 3 (94%) and the commonest histological types were ductal/no specific type (85%), and atypical medullary carcinoma (8%). High-grade comedo-type necrosis, lymphoid stroma, central necrosis/fibrosis and pushing margins were the most common morphological features. The presence of a pushing margin showed a significant relation to androgen receptor negativity, absence of epidermal growth factor receptor expression and negative lymph nodes. Lymphoid stroma and comedo-necrosis correlated with higher tumor grade. ER-negative breast cancers are a distinct group of tumors with several common morphological features. Grade 3 histology, pushing margin, lymphoid stroma, comedo-type necrosis and central fibrosis/necrosis are the dominant morphological findings. The presence of a pushing margin appears to have a significant correlation with negative lymph node status. ER-negative tumors show a higher expression of p53, CerbB2 and epidermal growth factor receptor compared to ER-positive breast cancer. These unique features support the concept that ER-negative tumors are a morphologically and phenotypically distinct entity and provide a rationale for the study and use of newer promising agents in the treatment of ER-negative breast cancer.
 ...
PMID:Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis. 1533 92

The aim of this study was to assess the morphological characteristics and immunohistochemical profile of breast carcinomas with basal and myoepithelial phenotypes to obtain a better understanding of their biological behaviour and nature. One thousand nine hundred and forty-four invasive breast carcinomas were examined, using tissue microarray (TMA) technology and immunohistochemistry, to identify those tumours that showed basal and myoepithelial phenotypes, and their immunophenotype profile was characterized using a variety of markers. In addition, haematoxylin and eosin-stained sections of these tumours were studied for several morphological parameters. The findings were correlated with patient and tumour characteristics and outcome data. Tumours were classified into two groups: (1) tumours with basal phenotype [expressing one or both basal markers (CK5/6 and/or CK14)] and (2) tumours with myoepithelial phenotype (expressing SMA and/or p63). Group 1 was further subdivided into two subgroups: (A) dominant basal pattern (more than 50% of cells positive) and (B) basal characteristics (10-50% of cells positive). Group 1 tumours constituted 18.6% (8.6% and 10% for groups 1A and 1B, respectively) and group 2 constituted 13.7% of the cases. In both groups, the most common histological types were ductal/no specific type, tubular mixed and medullary-like carcinomas; the majority of these tumours were grade 3. There were positive associations with adenoid cystic growth pattern, loss of tubule formation, marked cellular pleomorphism, poorer Nottingham prognostic index, and development of distant metastasis. In addition, associations were found with loss of expression of steroid hormone receptors and FHIT proteins and positive expression of p53 and EGFR. The most common characteristics in group 1 were larger size, high-grade comedo-type necrosis, development of tumour recurrence, and absence of lymph node disease. Group 2 tumours were more common in younger patients and were associated with central acellular zones, basaloid change, and positive E-cadherin protein expression. Group 1 characteristics were associated with both reduced overall survival (OS) [log rank (LR) = 22.5, p < 0.001] and reduced disease-free interval (DFI) (LR = 30.1, p < 0.001), while group 2 characteristics showed an association with OS (LR = 5, p = 0.02) but not with DFI. Multivariate analysis showed that basal, but not myoepithelial, phenotype has an independent value in predicting outcome. Breast cancers with basal and myoepithelial phenotypes are distinct groups of tumours that share some common morphological features and an association with poor prognosis. The basal rather than the myoepithelial phenotype has the strongest relationship with patient outcome.
 ...
PMID:Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. 1642 94

B9L/BCL9-2, a novel beta-catenin-interacting protein, plays an important role in colorectal carcinogenesis by translocating beta-catenin to the nucleus and enhancing beta-catenin-T-cell factor-mediated transcription. To elucidate the role of B9L in breast cancers, we studied B9L expression in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast immunohistochemically and compared it to the immunohistochemical expression of known proteins involved in breast carcinogenesis. In breast tissues, B9L immunoreactivity was present exclusively in the nuclei of normal and neoplastic ductal cells. In DCIS, immunohistochemical B9L expression was significantly associated with the tumor nuclear grade, comedo necrosis and the expression of ErbB2/HER-2, c-myc and p53. In IDC, B9L expression was correlated with ErbB2/HER-2 expression and tumor nuclear grade only. In both DCIS and IDC, immunohistochemical B9L expression was not related to the expression of cytoplasmic beta-catenin. We demonstrated that nuclear B9L expression was closely associated with the high nuclear grade cancer phenotype and the expression of ErbB2/HER-2 in breast cancers.
 ...
PMID:Immunohistochemical expression of the beta-catenin-interacting protein B9L is associated with histological high nuclear grade and immunohistochemical ErbB2/HER-2 expression in breast cancers. 1730


<< Previous 1 2 3 4 Next >>