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)

Peptide growth factors are proteins that stimulate cellular proliferation by binding to specific cell membrane receptors. Evidence is accumulating that abnormal regulation of growth factors may contribute to carcinogenesis. The epithelial growth factors, EGF and TGF-alpha, which share the same receptor, EGFR, may play a pivotal role in the development and maintenance of head and neck cancer; preliminary studies concerning TGF-beta and IL-2 are inconclusive. There is increased production of TGF-alpha and EGFR mRNA in the majority of fresh tissues and cell lines from patients with SCCHN. This increase results from transcriptional activation of the gene(s). Therapies directed at the regulation of gene transcription may be useful in chemoprevention or modulation of disease. Nuclear studies that target up-regulated growth factor receptors may improve the ability to detect microscopic regional metastatic disease.
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PMID:The role of peptide growth factors in head and neck carcinoma. 140 94

In 1983, the German Breast Cancer Study Group (GBSG), sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer (pT1 pN0 M0). This was preceded by a three-year reviewing period because of some novelties of medical, juristical and ethical problems in the FRG. University and, in the majority, community hospitals participated, combining all together 69 different institutions. From 11/1983 to 12/1989, 1112 patients were recruited. From 1036 patients, 733 underwent breast preservation (71%) and 303 mastectomy (29%). The randomization rate was only 6%. In 268 patients (26%) the tumor size was less than or equal to 10 mm, in 765 patients (74%) 11 to 22 mm. In 129 cases, we subdivided the tumor grading II[3] into IIa and IIb. Moreover, the immunohistochemical detection of the transmembrane proteins EGFR, p-185 and p-148 by oncogene overexpression and c-myc oncogene were undertaken in 425 breast cancers. After tumorectomy (or wide excision) and a lower axillary dissection (at least eight lymph nodes) the breast was irradiated up to 50 Gy in 25 fractions. A boost of 12 Gy was given to the tumor bed. The medial located lymph nodes were also irradiated in case of medially or centrally tumors. Quality control was performed by pathological, radiotherapeutic and methodical reference centers. Significant correlations could be demonstrated between receptor status and tumor grading, patient age and grading, and tumor size and grading. The results emphasize the central role of tumor grading among the prognostic factors. Especially the differentiation of the Bloom and Richardson score II into IIa and IIb seems to play an important role. After a median follow-up of 41 months, the frequency of local recurrences (4.4%), regional recurrences (1%) and distant metastases (4.6%) was exactly the same in both treatment groups. In multivariate analysis, only tumor size and tumor grading had a significant impact on disease-free survival. 23 patients with tumor-involved margins had a higher recurrence rate (DFS 62% versus 85% after five years). Without any impact on DFS were the other conventionally evaluated prognostic factors: age, menopausal status, hormone receptor status, histological tumor type, tumor localisation, degree of differentiation, pleomorphism, mitotic index and degree of dissociation. Among the transmembrane proteins EGFR, p-185, p-148 and c-myc, only the impact of p-185 and EGRF positivity on DSF is significant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Breast preservation versus mastectomy in early breast cancer--1991 update of the GBSG 1--protocol and prognostic factors. The German Breast Cancer Study Group. 157 68

Gene amplification and related alterations in gene dosage were analyzed in a series of 34 cell lines derived from different human head and neck squamous cell carcinomas (SCCHN). INT2 gene amplification was observed in 62%, MYC gene amplification in 24%, and EGFR gene amplification in 21% of the cell lines. There was a strong correlation between EGFR gene amplification and increased copies of the ERBB2 gene on chromosome 17, suggesting a synergistic selection for these two genes either during cancer progression or in culture. Two abnormalities showed a significant correlation with clinical course: MYC gene amplification showed an inverse correlation with tumor recurrence (r = -0.44, p = 0.01), and a small increase in MYCL gene copies on chromosome I correlated with the presence of metastases (r = 0.61, p = 0.001). This altered MYCL gene dosage might represent a chromosome translocation rather than true gene amplification. In addition to gene amplification, 79% of the cell lines had increased copies of chromosome 8. Comparison of the cell lines with several of the corresponding primary tumors demonstrated that most gene amplifications were already present in the primary tumors, although some appeared de novo in cell culture. These studies indicate that gene amplification, especially of INT2, is a prominent abnormality in head and neck squamous cell cancer. Aneuploidy and chromosomal lesions other than gene amplification were also found to alter the dosage of several oncogenes specifically.
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PMID:Gene amplification and gene dosage in cell lines derived from squamous cell carcinoma of the head and neck. 138 84

The prognostic significance of EGFR (epidermal growth factor receptor) was studied in a cohort of 68 node-positive patients with breast cancer, who entered a controlled protocol of adjuvant therapy between February 1980 and June 1984. EGFR radioligand binding assay was carried out on frozen stored samples. Twenty five (37%) of 68 primary sites and 9 (41%) of 19 lymph node metastases assayed were EGFR-positive with a cut off value of 5 fmol/mg membrane protein; there is no statistical difference between the two distributions. EGFR was significantly correlated to ER and histological grade. EGFR-positive tumors and high levels of EGFR were mainly found in the ER-negative group of tumors (p = 0.008) and in histological grade III (p = 0.007). Fifty five patients could be followed for 40 to 92 months. EGFR was an independent prognostic factor for survival after 40 months (p = 0.05). EGFR+/ER- patients had the lowest survival probability, but statistical significance was not reached (p = 0.06). The EGFR phenotype appeared as a patients with different early outcome, with potential therapeutic implication especially in the group of ER-negative patients. These results emphasize the need for a standardized assay methodology and for further clinical studies, particularly in protocols where adjuvant hormonal therapy is prescribed on the basis of steroid hormone receptor status, in order to assess the respective prognostic worth of EGFR and ER (or PR).
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PMID:Prognostic value of epidermal growth factor receptor in node-positive breast cancer. 269 Sep 71

About one in three people in modern industrialised countries die of the consequences of malignant tumours or are found to carry an unsuspected one at the time of autopsy. Early resection of such lesions and appropriate adjuvant therapy is very effective in curing the disease. There is therefore a strong clinical incentive to find effective methods of early diagnosis, assessment of prognosis and treatment of neoplastic lesions and research on this topic is directed at a numerically significant medical problem. Recently it has been found that many human tumours show severe abnormalities in the expression of the CD44 gene which increase with progression to metastatic malignancy. By alternative splicing mechanisms this gene codes for a family of heavily glycosylated cell surface proteins involved in many important cellular activities. In neoplasia there is gross overexpression of various products of the gene associated with disorderly splicing, which can be detected in clinical samples with the sensitive technique of reverse transcription-polymerase chain reaction (RT-PCR). These disturbances begin early in the neoplastic process and can be detected in very small biopsy samples. It has also been shown that it is possible to achieve non-invasive diagnosis of malignancy by analysis of CD44 expression in exfoliated cells in body fluids and waste products. The potential significance of these observations for early diagnosis of symptomatic cancer and for screening of the population for asymptomatic lesions are readily seen and await further investigation. Separate work in our laboratory has succeeded in DNA-mediated transfer of metastatic capability through two rounds of transfection into non-metastatic tumour cells and a metastasis-associated human DNA fragment has been recovered from the transfectants and sequenced. Using primers designed to anneal to a coding region identified by computer analysis within the novel sequence, it has been shown with RT-PCR that it is heavily expressed in metastatic cancer tissues, but not in corresponding normal ones. This could be of value in assessing the prognosis of patients using small biopsy samples from their primary tumours and the potential of this sequence for such purposes and for possible therapeutic intervention is currently being explored. Recent work in several laboratories has shown that elevated expression of certain other specific growth factor genes, including c-met and EGFR, correlates with metastatic capability. Combined evaluation of such markers in further studies will in time give useful information on the prognosis of individual patients to guide therapeutic decisions and the implications of these recent advances for clinical practice and future research are discussed below.
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PMID:Deranged activity of the CD44 gene and other loci as biomarkers for progression to metastatic malignancy. 751 58

The expression of Cath-D c-erbB-2 and EGFR in breast cancer and its correlation of lymphatic metastases were studied in 277 cases by immunohistochemical technique. Positive staining of Cath-D was detected in 107 cases (38.62%), of which, 89 cases (83.17%) had documented metastasis in the lymph nodes. One hundred and seventy cases (61.38%) stained negative for Cath-D, of which 64 cases (37.64%) had detectable lymphatic metastases. There was a significant difference in the rate of the lymphatic metastases between the Cath-D positive and Cath-D negative groups (P < 0.0001). Fifty-six out of 107 Cath-D positive cases (52.34%) were c-erbB-2 positive as well. However, only 27 out of 170 Cath-D negative cases (15.88%) were c-erbB-2 positive. The positive rate of c-erbB-2 in Cath-D positive group was significantly different from that of Cath-D negative group (P < 0.0001). Among those 107 Cath-D positive cases, 49 cases (45.79%) were EGFR positive. Only 24 cases (14.12%) were EGFR positive among the 170 Cath-D negative cases. The positive rate of EGFR between these two groups was also significantly different (P < 0.0001). The results suggest that Cath-D status can be used as an indicator of the aggressiveness of the breast cancer. Breast cancer cases with a positive Cath-D staining are more likely to have lymphatic metastases and a poor prognosis. Therefore, alternative therapeutic strategies and close follow-ups are needed for these patients.
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PMID:[The expression of Cath-D, c-erbB-2 and EGFR in breast cancer and its correlation to lymphatic metastasis]. 765 92

Cytologic specimens (FNA) from 42 primary invasive ductal breast carcinomas and 22 matched specimens of cancer tissue were tested for EGFR status, PCNA index and vimentin expression by immunocytochemical staining, using an Extravidin-Biotin method, and their relationship with various prognostic factors was investigated. EGFR positivity, high PC10 score and vimentin positivity were significantly correlated with high histologic grade. The coordinate expression of EGFR, PCNA and vimentin was significantly associated with ER-negative breast carcinomas. A positive trend was observed between high proliferating tumours and EGFR expression. EGFR status and PCNA index were not correlated with axillary lymph node involvement, tumour size, age and menopausal status. Vimentin was preferentially expressed in tumours, with lymph node metastases. Co-expression of EGFR, PCNA and vimentin was determined in most cases. These data suggest that EGFR status, PCNA index and vimentin expression may be important for the prediction of biologically aggressive tumours.
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PMID:Relationship of epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and vimentin expression and various prognostic factors in breast cancer patients. 773 97

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative -59% none positive, 29% one positive, 12% two or more positive, vs. node positive -37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positive for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
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PMID:Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. 791 62

For the integration of new cell biological prognostic factors in daily clinical practice, we need to know not only their prognostic power with respect to prediction of relapse free and overall survival, but also their possible relation to response to endocrine therapy or chemotherapy in order to select adequate treatment for each patient. A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficult to predict the response to treatment accurately. A valuable prognostic factor can be a worthless predictive factor for endocrine therapy or chemotherapy, and vice versa. High tumour levels of ER, PGR, AR and PS2 protein predict a relatively good response to endocrine therapy, whereas EGFR positivity, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high u-PA levels indicate a good chance of a poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, whereas MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low risk patients and type of systemic treatment and can be used as targets for new treatment modalities.
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PMID:Prognostic factors and response to therapy in breast cancer. 801 96

EGFR is a member of the tyrosine kinase family of cell surface receptors with a wide range of expression throughout development and in a variety of different cell types. The receptor can transmit signals to cells: i) upon interaction with ligands such as EGF, TGF alpha, amphiregulin or heparin binding EGF, ii) upon truncation or mutation of extracellular and/or intracellular domains, iii) upon amplification of a basal receptor activity (in the absence of ligand) through cooperation with other cellular signaling pathways or nuclear events (e.g. expression of v-erbA). The activated EGFR can exert pleiotropic functions on cells, depending on their tissue origin and state of differentiation. Under certain conditions it can also contribute to neoplasia and development of metastases. Such conditions can exist upon aberrant receptor/ligand expression and activation (e.g. in the wrong cell; at the wrong time; in the wrong amounts). Aberrant signalling can also occur through constitutive EGFR activation. Oncogenic potential of EGFR has been demonstrated in a wide range of experimental animals. EGFR is also implicated in human cancer, where it may contribute both to the initiation (glioblastoma) and progression (epithelial tumors) of the disease. EGFR may influence key steps in the processes of tumor invasion and dissemination. Involvement of EGFR in tumor spread may indicate a potential use of this receptor as a target for antimetastatic therapy.
Cancer Metastasis Rev 1993 Sep
PMID:EGF receptor in neoplasia and metastasis. 828 12


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