Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have conducted two series of studies, a biochemical study and an immunocytochemical study, to investigate the role of epidermal growth factor receptor (EGFR) expression in primary breast cancer patients. In the biochemical study, a consecutive 115 patients were included and EGFR was measured by a competitive binding assay with multipoint Scatchard analysis. In the immunocytochemical study comprising 126 patients, EGFR status was determined by immunostaining with anti-EGFR antibody EGFR1. Several agreements were found from these two studies. EGFR status was inversely correlated with estrogen receptor (ER) status. No significant correlation was found between EGFR status and tumor size, nodal metastases, or the expression of c-erbB-2 protein. Ki-67 immunoreactivity, a cellular proliferation marker, was enhanced in EGFR positive tumors over EGFR negative tumors, suggesting a linkage of EGFR expression to cellular proliferative activity. Post-operative follow up showed that relapse-free survival for EGFR positive patients was significantly worse than that for EGFR negative patients, particularly in node-positive patients. Multivariate analysis demonstrated a significance of EGFR status as an independent prognostic indicator in primary breast cancer. The group expressing EGFR and c-erbB-2 protein indicated a particularly high risk for relapse.
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PMID:Role of epidermal growth factor receptor expression in primary breast cancer: results of a biochemical study and an immunocytochemical study. 791 67

p53 is a tumor suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth. Mutations in p53 gene are the most common genetic alterations in a several human cancers, including Non Small Cell Lung Cancer (NSCLC). However, up to now, the role of p53 in the tumour's behaviour and its progression has not been completely clear. We performed immunohistochemical staining for mutated p53 using two monoclonal antibodies, PAb1801 and PAb240, in fresh tumour specimens from 103 consecutive patients who underwent surgery for resectable NSCLC. PAb1801 detects both the normal and mutant form of p53, while PAb240 is specific only for the mutant form and recognizes a denaturation-resistant epitope located between aminoacids 156-335. Both antibodies showed a mainly nuclear staining in neoplastic cells but not in surrounding uninvolved lung tissues. 68 out of 100 (68%) and 37 out of 103 (35.9%) of the cases were positive with PAb1801 and with PAb240, respectively. Tumours from patients with hilar-mediastinal lymph node involvement showed a higher p53 expression, detected by PAb1801, than those without nodal metastases (p = 0.04). Moreover, tumours expressing more than 60% of positive cells with both antibodies showed a significant increase of nodal involvement (p = 0.1; p = 0.03). Furthermore, p53 expression was significantly related to post-surgical stage (p Tumor Stage) (p = 0.04). In addition, we did not find any correlation between p53 expression and proliferating activity evaluated by PCNA, Ki-67 and DNA flow cytometric cell cycle. In conclusion, the evaluation of p53 oncogene expression may identify individuals whose resectable NSCLCs have a more aggressive tumour behaviour.
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PMID:p53 expression in non small cell lung cancer: clinical and biological correlations. 810 Apr 13

In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with systemic IFN-alpha, were evaluated for a comparison of metastases before (40) and during (42) treatment. Representative cryostat sections were studied immunohistologically with a panel of monoclonal antibodies against differentiation antigens (HMW-MAA, K-1-2, NKI-beteb, M-2-10-15), progression markers (transferrin receptor, ICAM-1, VLA-2), histocompatibility antigens (HLA-A, B, C, HLA-DR) and the proliferation-associated nuclear antigen Ki67. We found an overall reduction of the proliferation-associated antigen Ki-67 (p < 0.01), and an increase in expression of HLA-DR (p < 0.05) and ICAM-1 (trend) during treatment. The intensity of expression of HLA-A, B and C antigens as well as pigmentation (p < 0.01) was found to be increased. Early progression (< or = 8 weeks after onset of treatment) was associated with a lack of phenotypic changes. The data suggest an independent modulation of proliferation, pigmentation, and antigen expression by systemic treatment of metastatic melanoma with IFN-alpha.
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PMID:Effects of systemic interferon-alpha (IFN-alpha) on the antigenic phenotype of melanoma metastases. EORTC melanoma group cooperative study No. 18852. 810 70

A new monoclonal antibody prepared against a fragment of Ki-67 antigen MIB, from Dianova, was applied for investigation of malignant melanomas of facial skin (25 cases) and the oral cavity (25 cases), which were routinely embedded in paraffin. The values of the Ki-67 index (expressed as a percentage of positive nuclei) were correlated with TNM characteristics of tumors and patient survival. Significant correlation was found between the Ki-67 index and the level of lymph node involvement (N value), the presence of distant metastases and the time of patient survival. A positive relationship between the Ki-67 value and tumor size was also observed although it lacked statistical significance.
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PMID:An application of MIB antibody to the retrospective study of melanomas of oral mucosa and facial skin. 813 62

Cryostat sections of ductal breast carcinomas obtained during surgery from 48 patients were subjected to an indirect immunostaining with an antibody against Ki-67 antigen (Dako). The primary reaction was visualized by the APAAP technique with new fuchsin as chromogen. The percentage of positively stained nuclei was correlated with tumor size, number of metastatic lymph nodes, presence or absence of metastases in distant organs as well as with patient's age. The best correlations were achieved when the data were considered separately within the groups with low, medium and high Ki-67 values. A possible significance of Ki-67 evaluation for the prognosis and therapy is discussed.
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PMID:Correlation between the occurrence of Ki-67 antigen and clinical parameters in human breast carcinoma. 840 73

Abnormal patterns of proliferation characterize the behavior of many tumors. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two cell cycle antigens which are expressed in proliferative states. Our study examines the prognostic value of these cell-cycle antigens in soft tissue sarcoma (STS). Paraffin-embedded primary tumor tissues from 185 patients (1980-92) were stained with the anti-PCNA antibody PC-10; 182 of these were stained with the antibody MIB-1 for Ki-67. Using PCNA (< or = 50; > 50%) and Ki-67 (< or = 10; > 10%) indices, we examined and compared metastasis-free survival (MFS) in a mixed-histotype group, as well as after subdivision into MFH and non-MFH groups. Fifty-seven patients developed metastases. The median follow-up for survivors was 6 (2-13) years. In the mixed series, the 2-year MFS for a PCNA index < or = 50 was 76%, and for an index > 50 56%. Survival predicted by Ki-67 index was comparable. PCNA index (but not Ki-67) strongly correlated with the incidence of metastasis in MFH tumors and predicted 2-year MFS of 81 vs 48%. In contrast, Ki-67 index (but not PCNA) strongly correlated with metastasis in non-MFH tumors and predicted 2-year MFS survival of 90 vs 45%. No correlation existed between PCNA and Ki-67 indices in the mixed histotype, MFH or non-MFH groups. In combination, a high PCNA and Ki-67 index correlated with poor survival, a high PCNA and lower Ki-67 index (or vice versa) with an intermediate survival, and low PCNA and Ki-67 indices with the best survival. The pattern of PCNA and Ki-67 expression raises the possibility of histotype specificity.
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PMID:Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in soft tissue sarcoma. Is prognostic significance histotype-specific? 854 44

Retinoblastoma protein (pRB) is the product of a tumour-suppressor gene (rb) mapped to chromosome 13q14. pRB acts as a control checkpoint at the G1 phase of the cell cycle, preventing cells from entering into the S phase. Mutational inactivation of both normal alleles leads to loss of pRB expression and the development of malignant neoplasms. Absence of pRB occurs in retinoblastomas, sarcomas and several other types of tumours. The potential role of pRB in the pathogenesis of cutaneous melanoma is unknown, and was the subject of this investigation. Formalin-fixed, paraffin-embedded sections of four cutaneous melanoma metastases, 17 primary invasive melanomas and 10 predominantly intradermal melanocytic naevi were studied. Monoclonal antibodies directed against pRB and Ki-67 antigen were used after microwave heating of sections to restore antigenicity. pRB was not detected in morphologically normal epidermal melanocytes. In five naevi, only scattered cells (1%) expressed pRB, whereas in the other five naevi, pRB expression was undetectable. In contrast, pRB was detected in all primary and metastatic melanomas (5-70% of cells). Expression was always localized to nuclei. Ki-67 expression was detected only in the melanomas, with both cellular staining and regional localization similar to that shown by pRB in 13 of the 20 melanomas studied with both antibodies. pRB appears to be expressed at higher levels in melanomas than in benign naevi. It therefore seems unlikely that loss of rb expression is an important factor in the pathogenesis of melanoma.
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PMID:Immunohistochemical expression of retinoblastoma protein in cutaneous melanomas. 854 40

A 25-year-old patient with a rapidly growing sarcomatoid carcinoma of the urinary bladder is reported. The diagnosis was made on the basis of extended atypical proliferations of spindle or pleomorphic cells in the area of pelvic floor and the radix of the penis. The tumor showed invasion of the blood and a high Ki-67 growth fraction up to 40%. Immunohistochemically, the reactions with antibodies against cytokeratin, EMA, and vimentin were positive, while negative results were obtained in reactions with antibodies against desmin, actin, PSA, S 100, human epithelial antigen (Ber-EP4), and cytokeratin 13. The differential diagnosis against myosarcomas, pseudosarcomatous lesions, and inflammatory pseudotumours is discussed. After radical surgery a pelvic recurrence and pulmonary metastases developed, which led to the patient's death 3 months later. This case shows that sarcomatoid carcinomas of the urinary bladder can be found even in young people.
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PMID:[Sarcomatoid carcinoma of the bladder in a 25-year-old man]. 857 May 63

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

Expression of the Ki-67 antigen was determined by immunohistochemical analysis of paraffin-embedded specimens from 242 patients with gastric adenocarcinoma and the prognostic value of Ki-67 immunoreactivity was compared with ploidy and S-phase fraction (SPF) obtained by DNA flow cytometry. A high percentage of Ki-67 immunostaining was associated with the intestinal type of cancer (p = 0.0002) and male sex (p = 0.003), but correlated only weakly with the SPF (rs = 0.343) and not at all with ploidy. The intestinal type of gastric carcinoma was more frequently aneuploid and had a higher SPF than diploid tumours (p < 0.0001 for both). While the SPF was associated with male sex and stage of disease, both ploidy and SPF were associated with nodal status and age. There was no association between SPF or ploidy and tumour location or the presence of distant metastases. Both SPF and ploidy correlated with survival according to the univariate analysis. In a multivariate survival analysis, the stage of disease, DNA ploidy and presence of distant metastases emerged as independent prognostic parameters. There was no significant difference in survival between patients having tumours with high and low Ki-67 labelling, neither in univariate nor in multivariate survival analyses. In patients with gastric carcinoma, the level of Ki-67 immunoreactivity added no prognostic information to that obtained by DNA flow cytometry.
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PMID:Ki-67 immunoreactivity, ploidy and S-phase fraction as prognostic factors in patients with gastric carcinoma. 864 19


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