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)

To investigate HER-2/neu oncoprotein immunoreactivity, monoclonal antibody TA1 immunohistochemical examination of flash-frozen radical prostatectomy specimens was performed (n = 35). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or prostatic intraepithelial neoplasia (PIN), as well as prostatic carcinoma (CaP). HER-2/neu oncoprotein immunoreactivity in BPH tissues was not significantly different than that for the PIN basal cell layer (P = 0.10) or for the PIN luminal cells (P = 0.17). There was significantly more HER-2/neu oncoprotein immunoreactivity in BPH than in areas of CaP (P < 0.001). There was no significant difference in the amount of immunoreactivity present in PIN basal cells when compared to the PIN luminal cells (P = 0.49). Both the PIN basal cells and luminal cells stained for the HER-2/neu oncoprotein to a higher degree than cells in the CaP areas (P < 0.001 in both cases). HER-2/neu oncoprotein immunoreactivity is present at a significantly higher degree in BPH and PIN than in malignant prostatic epithelium.
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PMID:Differential immunoreactivity of her-2/neu oncoprotein in prostatic tissues. 128 16

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.
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PMID:The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials. 752 57

The most efficient strategy for chemoprevention clinical trials are short-term studies which focus on surrogate endpoint biomarkers (SEBs) in high-risk target populations. High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer, and is found in a significant number of routine contemporary needle biopsies without cancer. The frequency and extent of PIN are decreased with androgen deprivation therapy, suggesting that it is a suitable endpoint biomarker for modulation. Potential SEBs for screening chemopreventive agents for prostate cancer in short-term Phase II trials include (1) histologic premalignant lesions, such as high-grade PIN; (2) biochemical markers, including prostate-specific antigen (PSA) serum concentration; and (3) morphometric markers, including nuclear texture, shape, and roundness; size and number of nucleoli; and number of apoptotic bodies; (4) proliferation markers, including MIB-1 and PCNA; (5) genetic markers, including nuclear DNA content (ploidy), oncogene c-erbB-2 (HER-2/neu) expression, fluorescence in situ hybridization for chromosome 8; and PSA-producing cells in the blood detected by reverse transcriptase polymerase chain reaction; and (6) differentiation markers, such as microvessel density as a determinant of angiogenesis. Each of these endpoint biomarkers is measured easily and accurately in serum or in tissue specimens such as formalin-fixed, paraffin-embedded needle biopsies, and may be modifiable by intervention. The clinical utility of these biomarkers as modulatable endpoints in prostate cancer chemoprevention needs to be demonstrated in future clinical trials.
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PMID:Prostatic intraepithelial neoplasia (PIN) and other prostatic lesions as risk factors and surrogate endpoints for cancer chemoprevention trials. 902 13

Analysis of growth factors and receptors in putative premalignant lesions of prostatic adenocarcinoma should aid our understanding of their growth pathways. Sixty prostatic TURP (transurethral resection of the prostate) specimens exhibiting atypical adenomatous hyperplasia (AAH) and/or prostatic intraepithelial neoplasia (PIN) lesions were assayed by immunohistochemistry for androgen receptor (AR), epidermal growth factor receptor (EGFR), c-erbB-2, transforming growth factor-alpha (TGF-alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), MIB-1, E-cadherin, and high molecular weight keratin. Expression of these factors in the lesions was compared with that in the co-existing benign prostatic hyperplasia (BPH) or prostatic adenocarcinoma. Strong AR nuclear staining was observed in the luminal cells, but not the basal cells, of BPH and PIN lesions and in all the carcinomas examined. A similar growth factor and receptor profile was demonstrated in the secretory epithelium of high-grade PIN and carcinoma with a tendency to higher expression of membranous EGFR and c-erbB-2 and cytoplasmic TGF-alpha, and lower levels of FGF-2 than in low-grade PIN or BPH glands. Also, increased rates of proliferation, as estimated by MIB-1 stained cells, were observed in high-grade PIN in comparison with low-grade PIN and BPH and were not confined to the basal layer. AAH lesions resembled neither BPH nor carcinoma. Proliferation was virtually absent (MIB-1 expression); both AR and E-cadherin expression was significantly reduced; and, with the exception of FGF-2, all the other growth factors and receptors studied were absent. The results presented would support a premalignant role for high-grade PIN, whilst AAH would appear to represent a quiescent phenotype unlikely to progress to neoplasia.
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PMID:Expression of androgen receptor and growth factors in premalignant lesions of the prostate. 992 33

Chemoprevention is the administration of agents to prevent induction and inhibit or delay progression of cancers. For prostate, as for other cancer targets, successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating chemopreventive efficacy. Agent requirements are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the observed chemopreventive activity. On this basis, promising chemopreventive drugs in prostate include retinoids, antiandrogens, antiestrogens, steroid aromatase inhibitors, 5alpha-reductase inhibitors, vitamins D and E, selenium, lycopene, and 2-difluoromethylornithine. Phase II trials are critical for evaluating chemopreventive efficacy. Cohorts in these trials should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen as endpoints. Many cohorts proposed for phase II trials are patients with previous cancers or premalignant lesions. For such patients, trials should be conducted within the context of standard treatment. Two cohorts currently used in phase II prostate cancer chemoprevention trials are patients with PIN and patients scheduled for prostate cancer surgery. Biomarkers should fit expected biological mechanisms, be assayed reliably and quantitatively, measured easily, and correlate to decreased cancer incidence. Protocols for adequately sampling tissue are essential. Changes in PIN provide prostate biomarkers with the ability to be quantified and a high correlation to cancer. PIN measurements include nuclear polymorphism, nucleolar size and number of nucleoli/nuclei, and DNA ploidy. Other potentially useful biomarkers are associated with cellular proliferation kinetics (e.g. PCNA and apoptosis), differentiation (e.g. blood group antigens, vimentin), genetic damage (e.g. LOH on chromosome 8), signal transduction (e.g. TGFalpha, TGFbeta, IGF-I, c-erbB-2 expression), angiogenesis, and biochemical changes (e.g. PSA levels).
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PMID:Chemoprevention of prostate cancer: concepts and strategies. 1032 87

An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out. Thirty-seven men with the histologic diagnosis of prostate cancer planning to have radical prostatectomy entered the study after informed consent and were given 4-HPR (or matching placebo) as a single daily dose (two 100-mg capsules of 4-HPR or two capsules of placebo daily) for 3 weeks prior to surgery. Four men dropped out for unrelated reasons. Thirty-three men completed the study. At the time of surgery, repeat biopsies of the prostate were performed to study the effects of the drug on potential surrogate endpoint biomarkers (SEBs) of malignancy within the tissue. The panel of potential SEBs of malignancy include p53, cytomorphometric indices, ploidy, PNCA, erbB-2, erbB-3, EGF receptor, TGF-alpha tumor-associated glycoprotein-72, fatty acid synthetase and Lewis Y antigen. Twenty-three patients had matching pre- and posttherapy lesions and were considered informative. Results from the patients indicate significant differential expression of biomarkers in pretreatment specimens of uninvolved prostatic tissue (normal-appearing epithelia) prostatic intraepithelial neoplasia (PIN) and prostate cancer. The mean erbB-2 expression was 0.58 in uninvolved vs. 1.04 in PIN (p = 0.002); while the mean erbB-2 expression was 1.35 in prostate cancer (p = 0.0007, uninvolved vs. prostate cancer). A similar pattern of increased biomarker expression between uninvolved and PIN or prostate cancer tissues can be observed for EGF receptor (mean = 1.21, 1.87 and 1.76 for uninvolved, PIN and prostate cancer, respectively) and erbB-3 (mean = 0.81, 1.59 and 1.30 for uninvolved, PIN and prostate cancer, respectively). There were no statistically significant differences in biomarkers observed in the 4-HPR-treated patients when compared with placebo-treated control patients. There was a posttreatment up-regulation of biomarkers observed in both groups of patients. This observation is most likely explained by an effect due to the diagnostic sextant biopsy equally affecting both groups of patients. Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given.
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PMID:Evaluation of biomarker modulation by fenretinide in prostate cancer patients. 1032 1

There is scant information on the cell proliferation, apoptosis, oncogenes, and tumor suppressor genes status in adenosis. Forty-eight foci of adenosis were studied with immunohistochemistry for MIB-1; c-erbB-2, c-erbB-3, bcl-2 oncogenes; and p53. To evaluate apoptosis, the TdT dUTP nick end labeling (TUNEL) method was applied. Results were compared with the same studies on benign prostatic hyperplasia (BPH) (n = 20), low-grade prostatic intraepithelial neoplasia (PIN) (n = 10); high-grade PIN (n = 20), Gleason sum 2 to 6 cancer (n = 16); and Gleason sum 7 to 10 cancer (n = 22). MIB-1 proliferation index was lowest in BPH, followed by adenosis, low-grade prostatic intraepithelial neoplasia (PIN), low-grade cancer, high-grade PIN, and high-grade cancer. The apoptotic rate was generally low in all groups, although it was higher in PIN and cancer. In BPH and adenosis, bcl-2 was absent in luminal cells. In low- and high-grade PIN, both basal and luminal cells expressed bcl-2, whereas in cancer, expression was found in only 1 case (3%). C-erbB-2 showed absent or low values for cancer and adenosis, whereas it was commonly expressed in BPH and low- and high-grade PIN. Low expression in adenosis was also found with c-erbB-3 (6%) compared with all other groups. Expression of p53 was confined to cancer. Despite a significantly higher proliferation index rate compared with BPH, adenosis showed a markedly lower proliferating index when compared with low-grade PIN, high-grade PIN, and cancer. Expression of the oncogenes c-erbB-2 and cerbB-3 was very low in adenosis, and the staining pattern for bcl-2 was similar to that of BPH. These results provide additional evidence to that of prior studies that adenosis is a histological small acinar proliferation more akin to BPH than high-grade PIN or adenocarcinoma.
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PMID:Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer. 1049 43

Isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on needle biopsy confers an increased risk of prostate carcinoma (CaP) on follow-up biopsy. The aim of this study is to determine whether paraffin-section fluorescence in situ hybridization (FISH) of specific chromosome/oncogene copy number abnormalities (CNAs) in biopsy specimens with isolated HGPIN increases the predictive value for CaP on repeat biopsy. Cases were divided into 3 groups: controls (n=8) and sextant biopsy specimens with isolated HGPIN without CaP (group A; n=11) and with CaP (group B; n=14) on follow-up biopsy. Dual-color FISH assessing c-myc, HER-2/neu, chromosome region 7q31 (D7S486), and corresponding chromosome centromeres was performed. An amplification ratio (AR) for each marker centromere was derived for each biopsy specimen, with AR ranges designated as no/low, low-intermediate, and high. Also calculated for each marker were the percentage of cells with marker amplification, hyperdiploidy, and monosomy. A composite score for each biopsy specimen was calculated based on these parameters, with a possible range of 0 to 15. The specific chromosomal oncogene CNAs were as follows: for chromosome 7/7q31, 2 of 11 (18%) in group A and 6 of 14 (43%) in group B; for chromosome 8/c-myc, 4 of 11 (36%) in group A and 9 of 13 (69%) in group B; and for chromosome 17/HER-2/neu, 10 of 10 (100%) in group A and 13 of 14 (93%) in group B. The mean composite score was 0 for controls, 2.5 for group A, and 4.7 for group B. Composite scores > or =4 for the 3 groups were 0 of 9 (0%) for controls, 1 of 11 (12%) for group A, and 8 of 14 (57%) for group B. These differences were statistically significant (P=0.015). One group A patient with a high composite score (6) had atypical small glands on follow-up biopsy at <1 year. Chromosome/oncogene CNAs are uncommon in control patients, occurring with increasing frequency and magnitude in patients with isolated HGPIN without and with follow-up CaP. Chromosome/oncogene CNAs in HGPIN are mostly of the low to intermediate level and display intercellular heterogeneity. HER-2/neu amplification is common in HGPIN with and without follow-up CaP. Chromosome 7 and 8 aneusomy and 7q31 and c-myc amplification are greater in HGPIN with follow-up CaP. Patients with isolated HGPIN and high composite score without follow-up CaP are uncommon; these patients may have a small, unsampled CaP. Although patients with HGPIN without CaP are more likely to have a low composite score, a subset of patients with follow-up CaP have low composite score, suggesting (1) mutational pathways independent of chromosomes 7, 8, and 17 and HER-2/neu, c-myc, and chromosome region 7q31 CNAs; (2) CaP derived from an independent, unsampled focus of HGPIN; or (3) CaP not derived from HGPIN.
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PMID:Use of interphase fluorescence in situ hybridization in prostate needle biopsy specimens with isolated high-grade prostatic intraepithelial neoplasia as a predictor of prostate adenocarcinoma on follow-up biopsy. 1501 83