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)

Analyses of the level of expression of the epidermal growth factor receptor (EGF-R) of breast cancer tumours may add independent information about the prognosis for individual patients. Furthermore, the use of monoclonal antibodies directed against EGF-R as therapeutic tools (e.g., Mab 425) requires a reliable evaluation of the individual EGF-R content. Various analytical methods have been published, including (1) biochemical detectonn of EGF-R by a radiolabelled physiological ligand, (125I)EGF, (2) enzymatic analyses of EGF-R content (IEMA), (3) immunological analyses of EGF-R content with a monoclonal antibody (ELISA), and (4) immunohistochemical EGF-R detection. Studies with immunohistochemical analyses of EGF-R overexpression in formalin-fixed, paraffin-embedded tumour samples are rare. In a retrospective study, we examined the clinical data from 142 patients and the EGF-R expression in their formalin-fixed, paraffin-embedded tumour samples. The average follow-up was 69 months. EGF-R expression was compared to oestrogen (ER) and progesterone (PgR) receptor expression, histological grade, tumour size, lymph node metastases and menopause. 52 of 142 tumours were EGF-R positive. EGF-R overexpression correlated with high tumour grade, large tumours and elevated numbers of lymph node metastases. There was no significant correlation between ER or PgR and EGF-R expression. Determination of EGF-R overexpression revealed no significant difference in disease-free interval (DFI) or overall survival (OS). In this study, the determination of EGF-R in formalin-fixed, paraffin-embedded tumour samples proved feasible. Unfortunately, this did not add any additional information concerning DFI or OS.
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PMID:[Immunohistochemical detection of epidermal growth factor receptor (EGF-R) in paraffin sections of breast carcinoma tissue: correlation and clinical significance]. 760 82

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.
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PMID:Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: double-differential polymerase chain reaction (ddPCR) for clinical diagnosis. 760 71

Overexpression of members of the type 1 receptor tyrosine kinase (c-erbB) family has been documented in many types of cancer. In the case of c-erbB1 (epidermal growth factor receptor) and c-erbB2, this has been closely linked with poor prognosis, and in particular is apparently associated with an invasive/metastatic phenotype and relative insensitivity to conventional therapies. The cell surface location of these molecules renders them attractive targets for a variety of immunotherapeutic strategies, some of which are showing promise in preclinical and early clinical trials.
Invasion Metastasis
PMID:Significance of the c-erbB family of receptor tyrosine kinases in metastatic cancer and their potential as targets for immunotherapy. 765 27

The purpose of this study was to determine whether liver regeneration induced by partial hepatectomy (PH) influences the growth of human colon cancer (HCC) cells implanted into athymic nude mice. HCC KM12C cells were injected subcutaneously into nude mice and then the mice were randomized to undergo PH, laparotomy, or no surgery. The latent period to development of measurable tumors was shorter and the growth rate of HCC tumors was significantly faster in hepatectomized mice. Accelerated tumor growth directly coincided with liver regeneration. Peak mitotic activity in both the regenerating liver and HCC occurred on the second day following PH. No enhancement in growth of tumors occurred in mice implanted with HCC cells 3 weeks after PH (i.e. 2 weeks after completion of liver regeneration). The accelerated tumor growth was specific to HCC. We base this conclusion on results of control experiments where cells from human melanoma, colon, breast, prostate, and renal cancer were injected into nude mice that were then randomized to undergo PH or laparotomy. Only HCC grew faster in hepatectomized mice. No significant differences in expression of epidermal growth factor receptor (EGF-R) and c-met were found between HCC tumors in mice with PH or laparotomy, suggesting that over-expression of EGF-R or c-met is not an essential component of this phenomenon. The accelerated growth of HCC cells at a site distant from surgical trauma suggests that circulating growth factors involved in liver regeneration can specifically stimulate the growth of HCC cells.
Invasion Metastasis
PMID:Accelerated growth of human colon cancer cells in nude mice undergoing liver regeneration. 765 29

Elective cervical lymphadenectomy often is performed for laryngeal carcinoma to eliminate metastatic disease that escapes clinical and radiographic detection. We investigated characteristics of the primary tumor that might predict cervical lymph node status. We obtained archival tissue from 88 laryngectomies--65 with concurrent cervical lymphadenectomies. Of the 40 clinically negative necks that were dissected, 17% showed lymph node metastasis by pathologic examination. The primary tumors were examined immunohistochemically for expression of epidermal growth factor receptor (EGFR), p53, cathepsin D, proliferating cell nuclear antigen (PCNA), and Ki-67-specific antigen, and by flow cytometry for DNA ploidy-cell cycle analysis. Seventy-seven percent of the cases showed aberrant p53 staining, 99% expressed EGFR, 40% produced cathepsin D, 29% were aneuploid, and 54% had a moderate or high synthesis phase fraction (SPF). High grade, aneuploidy, and tumor vascular invasion independently predicted cervical node metastasis (p < .04 each). Supraglottic locale (p < .16) and a raggedly infiltrating invading margin (p < .13) were weakly associated with node positivity. Advanced clinical T status, the expression of EGFR, p53, and cathepsin D, the PCNA and Ki-67 indices, and SPF did not correlate with node metastasis. The presence of cervical node metastasis predicted poor disease-free (p < .005) and overall survival (p < .04). Advanced clinical T status correlated with brief overall survival (p < .02). Tumor site, histopathologic parameters, ploidy, SPF, PCNA and Ki-67 indices, and the expression of p53, EGFR, and cathepsin D did not affect survival. The presence of vascular invasion, high grade, and aneuploidy may help identify which patients would benefit from elective cervical lymphadenectomy. The correlation of cervical lymph node status and clinical T category with survival confirms the results of previous studies.
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PMID:Cervical lymph node status and survival in laryngeal carcinoma: prognostic factors. 766 16

The epidermal growth factor receptor and its ligands have been implicated as being involved in normal mammary development and breast cancer genesis. Northern blotting was used to assay the mRNA levels of the epidermal growth factor receptor and three of its ligands: the epidermal growth factor, the transforming growth factor alpha and the Amphiregulin in 16 primary carcinomas, 2 metastases and 5 fibroadenomas. In addition, the mRNA levels of the other members of the epidermal growth factor receptor family, erbB2 and erbB3 were also analysed. We found limited expression in the breast carcinomas while all the fibroadenomas showed expression at high levels. Therefore we suggest that the epidermal growth factor receptor plays an important role in the development of fibroadenomas. The erbB2 and erbB3 were more strongly expressed than the epidermal growth factor receptor in the primary carcinomas. This suggests that they could be of importance in breast carcinogenesis.
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PMID:High expression of the EGFR in fibroadenomas compared to breast carcinomas. 784 1

Differential reactivity for cathepsin D (cath-D) and epidermal growth factor receptor (EGFR) was compared in 102 archival cases of human primary prostatic carcinoma and nine prostate carcinoma metastases by immunohistochemical techniques using commercially available antibodies (Ciba-Corning, Triton Diagnostics Division, Alameda, CA). Western immunoblotting confirmed that the anti-cath-D and anti-EGFR antibodies recognized the appropriate-sized proteins in extracts of human prostatic carcinoma cell lines. For immunohistochemical analysis, the primary prostate carcinomas ranged from Gleason's combined scores of 2 to 9. High-grade prostatic intraepithelial neoplasia was coexistent in 79 of the cases. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). Heterogenous moderate to strong reactivity with anti-cath-D was detected in 96 of 102 cases of primary prostate carcinoma (94%), with a mean H score of 176.5. EGFR reactivity was much less common and less strong, with 41 of 102 primary prostate carcinomas staining (40%) at a mean H score intensity of 29.2. The immunohistochemical (H) scores of cath-D and EGFR reactivity both significantly correlated with the Gleason's combined score of the tumors. There was no significant correlation between the cath-D and EGFR scores. Ninety-nine percent of the examples of prostatic intraepithelial neoplasia were reactive with anti-cath-D, with no clear correlation between the intensity of staining of prostatic intraepithelial neoplasia and the adjacent carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of cathepsin D and epidermal growth factor receptor in prostate carcinoma. 789 62

The association between epidermal growth factor receptor (EGFR) expression, clinicopathological variables, silver-stained nuclear organizer region (Ag-NOR) counts, and patient survival was determined in 93 patients with operable breast cancer. The EGFR expression was found to be significantly associated with the presence and number of axillary lymph node metastases (P = 0.0429), but not with age, menopausal status, tumor size, histologic type or grade, or Ag-NOR counts. In a univariate analysis, a significant difference was also observed in the survival of patients stratified by tumor size (P = 0.0091), histologic grade (P = 0.0352), axillary lymph node metastases (P = 0.0001), and EGFR expression (P = 0.0263). However, a multivariate analysis revealed that axillary lymph node metastases was the only strong independent predictor of survival (P < 0.0001). When axillary lymph node metastases were excluded from the Cox model, the EGFR expression tended to be an independent prognostic factor (P = 0.0558). The results of this study thus indicate that the prognostic value of EGFR expression is limited because the EGFR expression is significantly associated with axillary lymph node metastases.
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PMID:The prognostic significance of epidermal growth factor receptor expression in breast cancer. 789 86

Expression of four biologic markers was studied in 69 cases of endometrial cancer to identify their association with cell type, decreased survival, and increased tumor metastasis. Cell types included endometrioid (n = 45), serous papillary (n = 16), and clear cell (n = 8). Immunohistochemical stains were employed to detect the presence of epidermal growth factor receptor (EGFR), HER-2/neu, p53, and proliferating cell nuclear antigen (PCNA). Analysis revealed that EGFR was expressed in 49%, HER-2/neu in 59%, p53 in 9%, and PCNA in 16% of tumor specimens. HER-2/neu overexpression was significantly associated with depth of myometrial invasion. p53 and PCNA immunoreactivity significantly correlated with nonendometrioid histology, although PCNA was less specific in labeling these less favorable cell types. EGFR immunoreactivity also significantly correlated with nonendometrioid cell types and tumor metastases at time of diagnosis. Seventy-seven percent of patients with metastatic disease were EGFR-positive versus 36% positivity in patients with no evidence of metastases (P < 0.002). For patients with endometrioid adenocarcinoma, evidence of EGFR overexpression decreased survival from 89 to 69% (P < 0.04). In the serous papillary and clear cell category, EGFR positivity decreased survival from 86 to 27% (P < 0.03). EGFR strongly correlates with tumor metastasis and patient survival in endometrial cancer. Altered expression of this oncoprotein may serve as a guide to prognosis and treatment in these patients.
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PMID:Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. 790 88

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


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