Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the c-erbB-2 oncoprotein (ErbB-2) and the nm23 anti-metastatic gene product (nucleoside diphosphate [NDP] kinase) was examined in the intraductal and invasive components of 63 fresh human breast cancer tissues. The expression of estrogen receptor (ER) as a marker of hormone dependency and the Ki-67 protein as a proliferative cell marker was also examined. ErbB-2 and ER were positive in 77.8% (28/36) and 64.7% (22/34) of the intraductal components, and in 43.6% (27/62) and 57.1% (36/63) of the invasive components, respectively. NDP kinase was positive in 58% (18/31) of intraductal, and in 30.9% (17/55) of invasive areas. The average Ki-67-positive cell rates were 5.9% in the intraductal, and 10.7% in the invasive components. Thus, the cells within the intraductal component of breast cancer appear to have different characteristics from the invasive component, not only in markers of proliferative ability, but also in the expression of oncogenes and hormone receptors.
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PMID:Estrogen receptor, c-erbB-2 and nm23/NDP kinase expression in the intraductal and invasive components of human breast cancers. 135 59

To examine the suggested biological difference between Japanese and British gastric cancers, immunohistochemistry was used to demonstrate eight markers of biological activity in a matched series of 40 Japanese and 33 British cases. There were no differences in the proportions of Japanese and British tumours positive to epidermal growth factor, epidermal growth factor receptor, transforming growth factor alpha, cripto or p53. A significantly greater proportion of British tumours were positive to c-erbB-2 whilst a significantly greater proportion of Japanese tumours were positive to nm23. British tumours had a significantly greater mean proliferating cell nuclear antigen proliferation index than Japanese tumours. These differences could be clinically significant.
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PMID:Are Japanese and European gastric cancer the same biological entity? An immunohistochemical study. 754 52

Immunophenotypes of mammary (MPD) and extramammary Paget's disease (EPD) are still not well understood. Thirty-four formalin-fixed paraffin-embedded tissue sections from 33 patients with 6 MPD and 28 EPD were studied immunohistochemically with the use of polyclonal c-erbB-2 and pS2 antisera, and monoclonal nm23, B6.2, GCDFP-15, and p53 antibodies. Cases of MPD expressed a high incidence of c-erbB-2 and nm23 compared with those of EPD (100% vs. 29%; p < 0.01, and 83% vs. 29%; p < 0.05, respectively). Although high expression of B6.2 (> 83%) and moderate expression of GCDFP-15 (33-39%), pS2 (33-46%) and p53 (39-50%) were seen, the positivity was not significantly different between MPD and EPD. These findings indicate that MPD and EPD share immunohistochemical features but partially differ in their patterns of antigen expression.
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PMID:Immunohistochemical study of mammary and extramammary Paget's disease. 776 23

To verity the role of metastasis-related nm23 genes in carcinogenesis and progression of ovarian carcinoma, we analyzed the mRNA levels of the nm23 genes of both isoforms, -H1 and -H2, together with those of the epidermal growth factor receptor, the c-erbB-2, and the c-erbB-3 genes in 45 ovarian carcinomas and 5 benign cystadenomas. Expressions of nm23 gene products/nucleoside diphosphate kinases, epidermal growth factor receptor, erbB-2 protein, and sex steroid receptor status in ovarian carcinomas were also examined by immunohistochemistry. The mRNA levels of nm23-H1 and nm23-H2 were higher in carcinoma tissues compared with benign tumors (H1, P < 0.01). The mRNA levels of c-erbB-2 and c-erbB-3 were also elevated in carcinoma tissues, and there was a positive correlation between mRNA levels of the nm23-H1 and the c-erbB-2 genes (r = 0.58; P < 0.05). Correlation of immunohistochemical staining between nucleoside diphosphate kinases and erbB-2 protein was also observed in ovarian carcinoma tissues. Sex steroid receptor positivity was related to a higher expression of nucleoside diphosphate kinases. Expression levels of the nm23 genes in ovarian carcinomas were not related to either histological subtype or local extension and peritoneal dissemination. Among stage III ovarian carcinomas, however, tumors possessing lymph node metastasis showed significantly lower nm23-H1 mRNA levels than those without nodal involvement (P < 0.05). Stage IV carcinomas also exhibited lower nm23-H1 and nm23-H2 expression levels compared with other stages (P < 0.05). These results suggest that expression of the nm23 genes, especially nm23-H1, is activated, accompanied by c-erbB-2 and c-erbB-3 overexpressions, in early stages of the carcinogenic process of ovarian carcinoma and reduction of nm23-H1 expression occurs in association with lymph nodal and/or distant metastasis.
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PMID:Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. 790 45

The nm23 gene is a potential metastasis-suppressor gene originally identified in a murine melanoma line. Several investigators have reported the probable inverse association of nm23 expression with disease prognosis and/or metastasis. Since there are now 2 known isotypes of human nm23, namely nm23-HI and -H2, we immunohistochemically examined expression of these isotypes in human breast-cancer tissues using monoclonal antibodies (MAbs) specific for each isotype protein. We also analyzed expression of c-erbB-2 in the same collection of cancer tissues, in order to examine the significance of nm23 expression in comparison with c-erbB-2 expression. Of 130 tumors from breast-cancer patients, 73 (56%) and 69 (53%) positively expressed nm23-HI and -H2 respectively. Expression of c-erbB-2 was positive in 36 (28%). Expression of nm23-HI, but not nm23-H2, was inversely associated with lymph-node metastasis (p < 0.01). Expression of c-erbB-2 was associated with Tnm stage, tumor size and lymph-node metastasis (p < 0.01, p < 0.05 and p < 0.05 respectively). Overall survival was better (p = 0.014) in patients in whom expression of nm23-HI was positive than in those in whom it was negative. In multivariate analyses using a Cox's proportional-hazards regression model with 9 variables, nm23-HI showed the fourth greatest contribution to patient survival following lymph-node metastasis, Tnm stage and menopausal status. No significant contribution was shown for c-erbB-2 expression. nm23-HI, but not nm23-H2, may perform a role in disease prognosis in addition to its participation in cancer metastasis. It may have value for predicting long-term survival of human breast-cancer patients.
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PMID:Reduced expression of nm23-H1, but not of nm23-H2, is concordant with the frequency of lymph-node metastasis of human breast cancer. 810 31

Oncogenes (c-erbB-2, c-myc, and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene (nm23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c-erbB-2, c-myc, and int-2, and expression of RB, p53(mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm23-H1 allelic loss was also studied. c-erbB-2 and c-myc amplification, loss of RB expression, p53(mutant) expression, and nm23-H1 allelic loss were also found in non-invasive carcinoma. int-2 amplification was significantly correlated with lymph node status (P = 0.02) and a significant association was found between p53(mutant) expression and tumor size (P = 0.04). c-erbB-2 amplification was strongly associated with disease-free and overall survival in multivariate analysis (P = 0.002). All of the c-erbB-2 amplified cases and all but one of the int-2 amplified cases in node-positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogen-dependent proliferation.
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PMID:Analysis of oncogenes and tumor suppressor genes in human breast cancer. 810 20

Breast cancer is a complex but increasingly well-understood disease. Clearly, multiple alterations from normal mammary cells are required to achieve a transformed phenotype. Furthermore, there may be several possible alterations within broad categories that will produce the transformations leading to the malignant state. The specific set of alterations within a given cancer may thus provide necessary information about how it is unique and how it may best be treated. Several of the newer biologic markers of breast cancer may provide very specific treatment information. erbB-2 may predict for improved response to doxorubicin, rather than CMF. hsp 27 may predict for failure of doxorubicin. pS2 or EGFR may provide supplemental information predicting response to hormonal therapy. Each of these variables has strong evidence to support its use in this manner, but that evidence has been obtained on limited numbers of patients treated in a limited number of ways. The most established markers, with multiple studies indicating their prognostic benefit, are erbB-2, cathepsin D, and proliferation markers. Of the several proliferation markers there may be no one choice that is best. However, very clearly, any marker must be carefully assessed for appropriate cut-off values, and cut-off values established by one cohort of patients should be verified against another cohort of patients. The oncoproteins associated with cell cycle regulation (cyclin D, p53, Rb, and c-myc) have shown strong promise of providing important prognostic information. The limited studies to date indicate that these markers are independent of one another. Cell cycle regulation may be an area in which any defect may serve to deregulate the cell, and therefore several defects in one cell would be unlikely. The specific nature of the defect in a given cancer may be very important. With the advent of immunohistochemical methods to measure most of the markers, more information may become available. Finally, the burgeoning area of tumor-stromal interactions is replete with potentially important markers of cancer prognosis. The growth factors, which are marginally a part of this area owing to the probable importance of paracrine effects on cancer cell growth, have progressively developed a body of literature supporting their prognostic potential. However, they have rarely been studied in conjunction with the other aspects of tumor-stromal cooperation. The markers of metastatic potential, nm23 and angiogenesis, have been shown in small cohorts to have considerable prognostic import.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Overview of the biologic markers of breast cancer. 815 Jul 84

Twenty-four advanced (surgical stage III and IV) ovarian carcinomas and 15 borderline ovarian tumours were studied for the overexpression of nm23 and HER-2/neu (c-erb-B2) by means of immunohistochemistry on sections from routinely processed, paraffin-embedded, archival tumour blocks, using the NCL-nm23 and the NCL-CB11 monoclonal antibodies and the streptavidin-biotin-peroxidase technique. Significantly more advanced ovarian carcinomas (p = 0.034) expressed high levels of nm23 when compared to borderline tumours. HER-2/neu (c-erb-B2) expression, as could be expected, was also significantly more frequent in advanced ovarian carcinomas (p = 0.006). We were not able to find the previously reported association between nm23 and HER-2/neu overexpression in our tumours. Our results on nm23 overexpression in ovarian cancer are coincident with those previously reported using nm23-mRNA measurements on fresh ovarian tissues. Thus, ovarian carcinoma seems to belong to the group of tumours, like colon carcinoma and neuroblastoma, in which nm23 overexpression is associated with a more malignant phenotype. Immunohistochemistry performed on archival samples from ovarian carcinomas seems adequate for the demonstration of nm23 overexpression in ovarian cancer. This opens the possibility for larger studies on series of patients with a closed follow-up, which could help to establish the role of this gene in this kind of tumour.
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PMID:nm23 expression in advanced and borderline ovarian carcinoma. 870 36

The recent highlighted points in prognostic factors after breast cancer operation include: 1) the emergence of many genetic and biochemical markers, including c-erbB-2, int-2, EGFR, p53, nm23, LOH, E cadherin, s-phase fraction. The prognostic value of these factors is related to their role in cell cycle regulation, invasion/metastasis mechanisms, etc. The agents related to therapeutic effectiveness, namely p-glycoprotein, pS2, and bcl-2 may become important stratification factors when conducting clinical trials. Pathologic factors, like nodal status, however, are the most useful prognostic factors at the moment. Many newly developed prognostic factors should be examined by multivariate analysis and validated prospectively before clinical use.
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PMID:[Recent prognostic factors for breast cancer]. 912 98

We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to 50. Clinicopathological criteria including clinical stage, hormone receptor status, histological types, histological grades, and lymph node status, were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed. Immunohistochemical findings were assessed semiquantitatively. Correlation between clinicopathological criteria, survival data, and immunohistochemical findings have been made. Patients aged younger than 35 years with stage I to II disease had a shorter DFS (P = .03) than older patients. However, no other clinicopathological finding was associated with age. Neither was there association between age and c-erbB-2, p53, or nm23 patterns of expression. p53 positivity was associated with high histological grade (P = .003) and with progesterone receptor negativity (P = .045). Nm23 nuclear positivity was associated with early clinical stages (P = .011) and with absence of axillary lymph node metastasis (P = .007). p53 and c-erbB-2 overexpression were associated with shorter OS while nm23 nuclear positivity was associated with longer OS in univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or nm23 were potentially important prognostic factors in women aged 35 years or younger while p53 was associated with prognosis in women aged 36 to 50. Cox model analysis indicated that c-erbB-2 alone was associated with prognosis in women 35 years and younger, whereas p53 alone was associated with prognosis in 36- to 50-year-old women. These results suggest that breast cancer in the youngest women has some biological specificity.
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PMID:C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: immunohistochemical analysis and clinicopathologic correlation. 956 80


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