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)

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

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.
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PMID:The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group. 826 79

Immunocytochemical assays for EGFR were performed on frozen sections from breast carcinomas (n = 209). Results were evaluated by computer assisted image analysis to accurately define the percentage of immunostained surface and the mean optical densities. Thirty seven percent (n = 77/209) of the tumors were EGFR positive, but about one third of them were faintly reactive (35%). No significant relationship was observed between EGFR tumor content and patient age, tumor size, histological type, histoprognostic grade, or axillary lymph node status. A negative correlation was observed with the results of estrogen receptor immunocytochemical assays and a positive correlation with immunodetectable cathepsin D and Ki 67 antigen evaluated according the same method. No correlation was found with HER-2/neu protein, aneuploidy, nucleolar organizor region distribution, and nuclear morphometry, also assessed by image analysis. These results suggest that immunocytochemical assays assessed on frozen sections and evaluated by image analysis are suitable for current and standardized evaluation of EGFR which has been previously documented as a prognostic indicator in breast carcinomas.
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PMID:Epidermal growth factor receptor in breast cancer: correlation of quantitative immunocytochemical assays to prognostic factors. 836 21

Estrogen receptor positive ovarian cancer is often refractile to antiestrogen therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E2) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE driven reporter gene, and E2 stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression of the progesterone receptor gene (PR) even after addition of E2, and the protein products of the estrogen responsive genes HER-2/neu and cathepsin D were expressed at constitutive levels that were not regulated by E2. Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.
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PMID:SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens. 854 Dec 24

In summary, certain subgroups of DCIS appear not to require radiation. Corroboration of these results from retrospective reviews and prospective trials is necessary to confirm the safety and efficacy of individualized treatment strategies. Even though the current standard of treatment is (1) lumpectomy with radiation therapy, (2) mastectomy, or (3) mastectomy with reconstruction, it is possible in the future to say that patients with low-grade DCIS (the exact criteria to be defined) may be eligible for breast conservation without radiation, and all patients with high-grade DCIS or perhaps low-grade DCIS with necrosis would be treated best by lumpectomy plus radiation. It is possible that a small subgroup of patients may be best treated by mastectomy, or perhaps, as the results of B-24 become available, by radiation therapy plus tamoxifen. The use of tumor markers such as c-erbB-2, cathepsin D, and NM 23 may help us to better define these subgroups, but much study is necessary before a definite treatment strategy is reached.
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PMID:Controversies in the treatment of ductal carcinoma in situ. 861 Feb 62

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.
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PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

The immunohistochemical overexpression of p53 protein in 42 large bowel cancers was correlated to c-erbB-2, cathepsin D (CD) proteins and other clinical and prognostic parameters. p53 overexpression (found in 60% of specimens) was positively associated with cathepsin D staining in stromal cells from older patients and better differentiated colorectal carcinomas (G1 + G2). Cytoplasmatic staining of c-erbB-2 protein was found in 58% of cases. No staining was observed at the cell membrane level. Our findings suggest that lower p53 expression in G3 carcinomas may be due to a high genomic instability, with the loss of both alleles of the gene. Therefore, these carcinomas were immunohistochemically silent. Although our series was small, the association between p53 nuclear neoplastic cells and CD stromal cells is interesting as regards the possible implications of these markers in colorectal cancer.
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PMID:Immunohistochemical p53 overexpression correlated to c-erbB-2 and cathepsin D proteins in colorectal cancer. 904 63

The overexpression of c-erbB-2 protein (ErbB2), epidermal growth factor receptor (EGFR), and/or cathepsin D (CD) in breast cancer is known to be a poor prognostic factor. Eighty frozen breast cancer specimens obtained at the initial operation were examined for ErbB2, EGFR, and CD by immunohistochemical assay (ICA) and enzyme immunoassay (EIA). Estrogen and progesterone receptors (ER and PgR) were measured simultaneously by EIA. The mean values +/- 1SD for ErbB2, EGFR and CD were 141 +/- 400 U/mg membrane protein (range: 0-3385), 4.88 +/- 4.33 fmol/mg membrane protein (range: 0-21.1), and 47.1 +/- 32.8 pmol/mg cytosol protein (range: 4.7-182), respectively. The percentage of specimens positive for ErbB2, EGFR, and CD was 12.5, 38.8, and 35%, when the tentative cutoff value were used as 200 U/mg protein, 5 fmol/mg protein, and 50 pmol/mg protein, respectively. These E1A results were correlated with ICA, EGFR and ER were negatively correlated. Although the prognostic value of ErbB2 and EGFR was superior to hormone receptors, ErbB2 and EGFR were interior as predictors compared with lymph node involvement and tumor size. Quantitation of ErbB2, EGFR, and CD can be performed readily using the same specimen in which hormone receptors are measured.
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PMID:Simultaneous quantitative analyses of c-erbB-2 protein, epidermal growth factor receptor, cathepsin D, and hormone receptors in breast cancer. 904 60

Even among breast cancer patients without metastasis to axillary lymph nodes, early recurrence can occur. To determine the risk factors for early recurrence, we performed a case-control study between 32 patients with an early recurrence of breast cancer and 122 patients without recurrence, in which tumor size, age of patient and date of operation were matched. In all 154 node-negative patients, followed up over a 13.1-year median period, expression of p53, c-erbB-2 and cathepsin D in the primary tumor were studied immunohistochemically in paraffin-embedded tissues and were compared with morphologic factors such as histologic grade and invasive growth. Univariate analysis showed that nuclear p53 immunoreaction was significantly predictive of early recurrence [risk ratio (RR) 3.3]. Likewise, cathepsin D (RR 0.22) was significantly negatively associated; however, when the risk ratio was analyzed in terms of intensity of cathepsin D staining, no superior survival was found for patients with strongly positive tumors. Overexpression of c-erbB-2 protein was not associated with outcome by either univariate or multivariate analysis. As a whole, histologic grade was confirmed as being a strong predictor (RR 42.6) and multivariate analysis showed that only histologic grade was a significant risk factor for early recurrence. p53 immunoreaction was not a significant independent factor because it was closely linked to histologic grade (P = 0.002), especially to a high mitotic index (P < 0.001). Moreover, in 14 patients with "special histologic types' of invasive carcinomas and no recurrence, all were p53-negative except one medullary carcinoma. Nuclear p53 immunoreaction is useful in supporting histologic grade to detect a high-risk for early recurrence in node-negative patients who may be eligible for systemic adjuvant therapy.
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PMID:Histologic grade and p53 immunoreaction as indicators of early recurrence of node-negative breast cancer. 907 Mar 33

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from 'clinical' cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history.
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PMID:The pathological and biological nature of screen-detected breast carcinomas: a morphological and immunohistochemical study. 958 38


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