UMLS:C0027627 - FACTA Search

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The disease-free (DFS) and overall (OS) survival was retrospectively assessed using mono- and multiparametrical methods in 197 patients with T1-2N0-1M0 tumors of the breast during a 3-73 month follow-up. No significant differences in DFS or OS were observed between epidermal growth factor receptor(EGFR)-positive or negative patients, either in the general study group or in those without metastases in the lymph nodes. However, DFS was much and significantly higher in patients with an "endocrine" receptor phenotype of tumor (EGFR-ER+PR+) than with an "auto/paracrine" one (EGFR+ER-PR). The DFS difference was particularly pronounced within the first 48 months (up to 30%) and subsequently smoothed down. In early-stage breast cancers, ER and PR status-related studies alone failed to reliably identify the group with unfavorable prognosis. The study also failed to establish any correlation between either of the phenotypes and the relative hazard rate for DFS in cases of no post-surgical treatment or treatment lacking the endocrine component. Conversely, the risk of relapse and/or metastasis was markedly higher in tumor with EGFR, after adjuvant hormone or chemohormonal therapy. The correlation between the ER or PR-positive and negative patterns and risk of relapse were significantly lower.
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PMID:[Prognostic significance of epidermal growth factor receptors in stage I-II breast cancer: results of a six-year follow-up]. 980 98

Angiogenic growth factors are essential for cancer metastasis, and the growth of metastatic foci also depends on these angiogenic growth factors as well as autocrine or paracrine growth factors. We therefore investigated whether vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase) are localized more often in primary tumors with hepatic metastasis than in those without such metastasis and whether transforming growth factor (TGF-alpha) and epidermal growth factor receptor (EGF-R) are coexisted more often in hepatic metastases than in primary tumors of gastric cancer. Resected specimens from 82 patients with gastric cancer were examined immunohistochemically. The primary antibodies used were anti-VEGF, anti-dThdPase, anti-TGF-alpha and anti-EGF-R. VEGF expression was found to be higher in primary cancers with than in those without hepatic metastasis (p < 0.001), while VEGF was frequently observed in both hepatic metastases and in the primary tumors. Localization of dThdPase was also higher in advanced than in early gastric cancers (p = 0.021). High co-presence of TGF-alpha and EGF-R was detected more frequently in cancers with deep gastric wall invasion than in those without such invasion (p = 0.050), and also more often in cancers with venous invasion (p = 0.007) and those in the advanced stage (p = 0.020). Co-presence of TGF-alpha and EGF-R was found to be higher, though not significantly, in hepatic metastases (58.8%) than in primary tumors (29.4%). These findings suggest that localization of VEGF may play an important role in hepatic metastasis, and that the expression of VEGF, dThdPase and the TGF-alpha/EGF-R pathway may be responsible for the growth of hepatic metastasis.
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PMID:Immunohistochemical demonstration of angiogenic growth factors and EGF receptor in hepatic metastases and primary human gastric cancer. 980 88

Expression of epidermal growth factor receptor (EGFR) or of c-erbB2 in primary breast cancer has been shown to predict for a poor chance of subsequent response of recurrent/metastatic disease to endocrine therapy. To assess the role of these receptors in the development of tamoxifen resistance, we examined their expression immunohistochemically on paraffin-embedded sections from breast cancers from 155 patients whose disease was progressing on tamoxifen therapy. Patients were categorized into those who initially responded to therapy (n = 56), those who never responded (n = 39), and those who relapsed while on adjuvant therapy and may or may not have "responded" (n = 60). In 61 cases, pretreatment specimens were also obtained for direct comparison with the resistance specimen for each patient. None of the 18 pretreatment samples from patients who responded to therapy expressed c-erbB2, and 1 of 18 expressed EGFR. Of the nonresponders, 7 of 18 expressed EGFR pretreatment, and 4 of 18 expressed c-erbB2 (1 patient expressed both receptors). Results confirmed previous findings that when considered independently, expression of either receptor pretreatment tended to predict for a poor chance of response (EGFR, P = 0.046; c-erbB2, P = 0.11). Importantly, patients who were either EGFR positive and/or c-erbB2 positive had a much poorer chance of response than "double negatives" (response rates of 1 of 11 and 17 of 25, respectively; P = 0.0039). At the time of disease progression compared to pretreatment, there was no significant change in expression of either receptor, irrespective of initial response. The inverse relationship between EGFR and estrogen receptor was maintained at relapse on tamoxifen. These data argue strongly against the acquired expression of these receptors during treatment playing a major role in the development of tamoxifen resistance in human breast cancer.
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PMID:Expression of epidermal growth factor receptor and c-erbB2 during the development of tamoxifen resistance in human breast cancer. 981 55

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.
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PMID:Changing pattern of expression of the epidermal growth factor receptor and transforming growth factor alpha in the progression of prostatic neoplasms. 981 14

Papillary renal carcinomas are a cytogenetically unique subset of renal carcinomas that have been reported to be clinically less aggressive. We have examined 19 papillary tumors for immunohistochemical expression of the epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor alpha (TGF-alpha). EGF-R and TGF-alpha expression was also studied in 149 nonpapillary tumors and 7 mixed papillary/solid tumors. EGF-R and TGF-alpha expression were compared to histology, stage, metastatic behavior, and survival. Formalin-fixed, paraffin-embedded nephrectomy specimens collected between 1977 and 1986 were stained with antibodies to EGF-R and TGF-alpha. Patients with papillary tumors were found to present with earlier stage disease and had significantly longer survival. Papillary tumors had a significantly lower rate of EGF-R positivity than solid pattern tumors (21% versus 73%, P < 0.001). Intermediate or strong cell membrane immunoreactivity for EGF-R was associated with high tumor grade and poor disease-specific survival. EGF-R positivity in the primary tumor was associated with the presence of metastatic disease and with metastatic spread to lung versus bone. Tumor parenchymal TGF-alpha staining was present in 50% of the cases and was not associated with stage or grade. Unrelated to tumor parenchymal TGF staining, tumor vessels stained for TGF-alpha in 56% of the cases. Vessel TGF-alpha staining was absent in papillary tumors (P < 0.001). The improved clinical behavior of papillary tumors as compared to nonpapillary renal tumors may be related, in part, to their relatively lower levels of EGF-R expression.
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PMID:Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis. 981 62

Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.
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PMID:Expression of c-erbB3 protein in primary breast carcinomas. 982 84

The erbB-4 gene encodes a detected receptor protein that possesses intrinsic tyrosine kinase activity and belongs to the family of the epidermal growth factor receptor (EGFR); erbB-4 is stimulated by the heregulins and betacellulin, which enables this receptor to form heterodimers with erbB-2, a prerequisite for erbB-2 activation. Because the expression of erbB-4 mRNA is generally low in the pancreas, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the erbB-4 levels in human normal and cancerous pancreatic tissue. Our results show that the mRNA expression of this receptor is 6-fold decreased in the non-metastatic stages of pancreatic cancer when compared to tumors with lymph node or distant metastases or to the normal pancreas. In addition, immunohistochemistry demonstrated that in the normal pancreas, the erbB-4 antigen was predominantly present in the cell membrane and cytoplasm of the ductal and acinar cells and at a much lower level, in islet cells. In pancreatic cancer, 61 of 75 samples exhibited weak to moderate immunoreactivity for erbB-4 in the tumor cells. Moreover, in the peri-tumorous region with chronic pancreatitis-like morphological changes, there was weak-to-moderate erbB-4 immunostaining in small ductules and degenerating acinar cells. Uni- and multivariate survival analyses using as variables age, sex, stage of cancer, histo-pathological grading, and erbB-4 immunoreactivity, revealed a significant effect for stage of cancer (p < 0.01) whereby the risk of dying was 2.3 times higher in patients with metastases than in patients without. However, the level of erbB-4 immunoreactivity in pancreatic cancer cells had no influence on patient survival.
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PMID:ErbB-4 mRNA expression is decreased in non-metastatic pancreatic cancer. 998 27

Tumor metastasis is the main cause of mortality and treatment failure in cancer patients. It is a complex biological process regulated by alternations in expression of many genes. The p53 tumor suppressor gene has been shown to regulate expression of some metastasis-related genes. p53 transcriptionally activates expression of the genes encoding epidermal growth factor receptor, matrix metalloproteinase (MMP)-2, cathepsin D, and thrombospondin-1 but represses expression of the genes encoding basic fibroblast growth factor and multidrug resistance-1. Decreased expression of E-cadherin is associated with p53 alternations. Because these p53-regulatory genes either promote or inhibit tumor metastasis, the net effect of p53 expression on tumor metastasis depends upon the pattern of expression of these genes in a particular tumor. Because radiotherapy has been shown to increase tumor metastasis in both animal and human studies and because p53 is activated by radiation or DNA-damaging reagents, here we propose the working hypothesis that p53 may promote tumor metastasis upon induction by local radiotherapy or chemotherapy in some tumor types. For patients whose tumors contain wild-type p53, MMP inhibitors might be given with or before radiotherapy or chemotherapy to prevent an increase in tumor metastasis. Special caution should be taken with patients with cancers such as nasopharyngeal carcinoma in which p53 mutation is infrequent and radiotherapy is the main choice of treatment. To test our hypothesis, three studies are proposed and could serve as an initial step in understanding the complex biological process following radiation-induced p53 activation and its roles in regulation of tumor metastasis.
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PMID:Regulation of metastasis-related gene expression by p53: a potential clinical implication. 1002 7

Specimens of laryngeal squamous cell carcinoma (LSCC) were examined for epidermal growth factor receptor (EGFR) content using a radioreceptor method; 140 untreated consecutive patients with primary LSCC undergoing initial surgical resection were followed up for a median of 49 months (range 2-84 months) after surgery. Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels were directly associated with the risk of lymph node metastasis. A significant relationship between EGFR status and cervical node metastasis was observed. The cutoff value of 20 fmol/mg protein was the best prognostic discriminator. The 5-year metastasis-free survival (MFS) was 66% for patients with EGFR- tumors compared with 15% for patients with EGFR+ tumors. By multivariate analysis, the EGFR status appeared to be a significant independent prognostic factor for MFS. Our results suggest that the assessment of EGFR status at the time of diagnosis may identify a subset of LSCC patients highly susceptible to neck node metastases thus defining therapy accordingly.
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PMID:Epidermal growth factor receptor expression in primary laryngeal cancer: an independent prognostic factor of neck node relapse. 1009 53

The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established. However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have investigated the role of several (onco)genes in cervical carcinoma. In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor (EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases, tumor diameter, vessel invasion, and disease-free and overall survival. Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this expression was correlated to p53 expression (P<0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free (P = 0.002) and overall survival (P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph node status. Gene amplification was found for EGFR (four cases), c-erbB-2/ neu (two cases), and c-myc (six cases). In two tumors, rearrangement of c-myc was found, probably due to the integration of HPV. In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.
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PMID:Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis. 1010 Jul 9

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