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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of oncogene products related to cell growth (c-erbB-2, c-myc, ras p21, EGFR) was investigated in benign (15 cases) and malignant breast lesions (20 cases) by means of immunohistochemistry using the avidin-biotin-peroxidase technique with polyclonal and monoclonal antibodies. The aim of this study was to evaluate the relationship between the staining positivity and various morphological and biological features, such as tumour type, grading, hormone receptor status and cell kinetic parameters. In benign breast lesions, as expected, the kinetic parameters were low, both for Ki-67 and LI. All the specimens showed a diploid condition (the DI being equal to 1) and we found a limited degree of immunoreactivity for all the growth factors and oncogene products. In breast cancer we studied the distribution of immunohistochemical positivity for EGFR, c-erbB-2, c-myc, ras p21 and Ki-67, which was related to age, nodal status, ER and PgR receptor status, LI, DI and histopathological grading. A significant positive correlation was found both between ras p21 expression and nodal status and ER-ICA positivity. We observed a strong correlation between LI and Ki-67 and an inverse relation between Ki-67 and ER expression. These findings suggest the importance of studying the relationship between prognostic factors which may provide preoperative prediction in the biological behaviour of breast cancer, not only on biopsy specimens, but also on fine needle aspirates.
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PMID:Preliminary study on oncogene product immunohistochemistry (c-erbB-2, c-myc, ras p21, EGFR) in breast pathology. 134 7

The animal models for chemoprevention of breast cancer have provided important experimental systems to evaluate the efficacy of tumor suppression by dietary macro- and micronutrients. In the initiation/promotion cascade, early occurring premalignant changes constitute less extensively examined aspects of disease progression. Molecular, endocrine and cellular biomarkers may provide clinically relevant endpoints for prevention of breast cancer that focus on downregulation of preneoplastic transformation. In vitro models derived from non-involved murine and human mammary tissues are utilized to identify molecular, endocrine and cellular markers that are perturbed in response to such diverse initiators as viruses and chemical carcinogens. This upregulation was manifested as persistent Ras p21-GTP binding, altered C16 alpha/C2 hydroxylation of estradiol, and hyperplasia preceding tumorigenesis. Prototypic chemopreventive agents such as n-3 polyunsaturated fatty acids, retinoids, and indole-3-carbinol were capable of downregulating all of the preneoplastic markers perturbed by initiators. Experimental modulation of these biomarkers in murine and human mammary tissue prior to the expression of a fully transformed tumorigenic phenotype is suggestive of their potential clinical application in chemopreventive intervention for breast cancer.
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PMID:Molecular and endocrine biomarkers in non-involved breast: relevance to cancer chemoprevention. 146 96

The ras, Rb and p53 genes have been implicated in the development of human breast cancer. Qualitative or quantitative changes in the expression of the ras p21 may lead to cell transformation, and this has been previously demonstrated in breast cancer. Both the retinoblastoma protein (Rb1) and the p53 gene product appear to function as negative regulators of cell division. We have investigated the expression of ras p21, Rb1 and p53 proteins in human breast cancer patients immunohistochemically, and correlated the results with a range of clinical and pathological parameters. Ras p21 expression was elevated in 65 per cent and p53 in 23 per cent of cases. Rb1 was expressed in 58 per cent of breast cancer tissues and in 75 per cent of normal tissue. Only four patients were found to have loss of Rb1 expression and also overexpression of both p53 and ras gene products. No correlations were found between the expression of these three genes and menopausal status, histological types or tumour grade. However, a correlation was found between Rb1 loss of expression and tumour diameter (greater than 2 cms), and no lymph node metastasis. Also, a significantly higher number of p53 staining specimens were found to be overexpressing the ras gene. These results suggest that all three oncogenes are most likely involved in the development of breast cancer but that their role is complex.
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PMID:Expression of ras Rb1 and p53 proteins in human breast cancer. 156 85

For the purpose of demonstrating the relationship between the expression of ras oncogene p21 protein and clinico-pathological characteristics which reflected the prognosis, 253 women with breast cancer who underwent mastectomy were analyzed. Ras p21 was detected in 133 (52.6%). In histological types, scirrhous carcinomas were more often ras p21-positive, and papillo-tubular carcinoma were usually negative. And histological grade was significantly correlated with ras p21. The degrees of invasion to fat tissues and infiltration into lymphatic vessels were also significantly correlated with ras p21. Tumors with lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors in smaller tumors, especially in papillo-tubular carcinomas. And patients with elevated ras expression tended to have a poor prognosis. These results suggested that an elevated ras expression may play an important role in the development of aggressive tumors.
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PMID:[Expression of ras oncogene p21 in relation to prognostic factors of human breast cancer]. 165 90

Deregulated expression of the RAS oncogene is associated with tumorigenic transformation of mammary cells. Because of the complex, multiphasic nature of cancer progression, it is important to systematically identify the biomarkers specific for initiation, promotion, and progression of breast cancer. Mouse mammary epithelial cells (MMEC) were transfected with normal c-Ha-RAS proto oncogene (pH06N) and with mutant c-Ha-RAS oncogene (pH06T). The parental MMEC and the cloned transfectants pH06N1, pH06N2, pH06T1, and pH06T12 were evaluated for the acquisition of transformed characteristics by determining altered cellular metabolism of estradiol, increased ability for anchorage-independent growth, and ability to form tumors at the transplant site in athymic 'nude' mice. Persistent, functional integration of c-Ha-RAS was evidenced by the presence of a 1.2 kb c-Ha-RAS transcript in the four transfectants but not in MMEC. All the transfectants also exhibited a substantial increase in the binding of c-Ha-RAS p21 to [alpha-32P] GTP relative to MMEC (P less than 0.003). The relative extent of estradiol metabolism leading to the formation of 16 alpha-hydroxyestrone was increased (P less than 0.004) in all the four transfectants. These four transfectants also showed a 100-400 fold increase in colony forming efficiency in 0.33% agar, relative to MMEC (P less than 0.0009), and formed rapidly growing tumors within 3-5 weeks of transplantation. Our results demonstrate that i) persistent expression of normal and mutant c-Ha-RAS can bring about tumorigenic transformation of mouse mammary epithelial cells; and ii) alteration in estradiol metabolism and acquisition of anchorage-independent growth precede the emergence of a tumorigenic phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
Breast Cancer Res Treat 1991 Aug
PMID:Coordinated expression of intermediate biomarkers for tumorigenic transformation in RAS-transfected mouse mammary epithelial cells. 175 58

Cytogenic studies were performed in a 72-year-old male patient with triple primary cancers including breast, skin and lung. Left breast cancer was diagnosed at the age of 46 and he received mastectomy and thoracic irradiation. Squamous cell carcinoma and Bowen's disease were diagnosed from two separated parts of a skin lesion at the age of 70. Small-cell lung cancer was diagnosed 1 year later, and he received chemotherapy and radiotherapy. Chromosome analysis was carried out on both peripheral lymphocyte and skin fibroblast cultures at the age of 72. Out of 30 fibroblast cells karyotyped at the second passage, 7 cells (23%) consistently showed a reciprocal translocation t(Y;6)(q12;p21). The same translocation was found in one of 200 cells from lymphocyte cultures. The findings suggest that the translocation t(Y;6) might be inherent in nature, and that the patient was a mosaic of 46,XY/46,X,t(Y;6)(q12;p21). These results highlight the constitutional chromosomal abnormality as one of the possible high-risk factors for multiple primary cancers.
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PMID:Y/6 chromosome translocation in a male with triple primary cancers involving the breast. 189 Jan 41

The protein product of the H-ras oncogene, p21, has been measured semiquantitatively in solubilized particulate fractions of 160 primary tumours from patients presenting without evidence of distant metastatic breast cancer. Levels of p21 have then been related to factors of established prognostic significance, and to clinical outcome after primary treatment in terms of disease-free interval and survival times. p21 was detected by Western blotting in all tumour fractions, but amounts varied markedly between different tumours. There was no significant relationship between levels of p21 and the menopausal status of the patient, tumour oestrogen receptors, grade, and clinical stage. However, there was a significant trend for tumours to be associated with lymph node involvement as p21 was increasingly expressed. Elevated levels of p21 were also significantly related to early disease recurrence and death from cancer. Multivariate stepwise analysis showed that both p21 and lymph node status were independent statistically significant factors for disease recurrence and survival, and that no other parameter was significant for clinical outcome after adjustment for p21 and lymph node status. These results indicate that tumour levels of p21 are an important prognostic variable in patients with early breast cancer.
Breast Cancer Res Treat
PMID:The H-ras oncogene product p21 and prognosis in human breast cancer. 203 38

Activation of ras protooncogenes by any of several possible mutations in codons 12, 13 or 61 has been demonstrated in a variety of human malignancies, including acute non-lymphoblastic leukemia (ANLL). In situ staining for the ras gene product, p21, has been demonstrated in carcinomas of several sites. High levels of p21 expression have been associated with histologic anaplasia in prostate cancer and regional lymph node metastasis in breast cancer. We examined 16 marrow aspirates and blood smears from patients with acute leukemia, predominantly ANLL, and eight controls. Marrow aspirates or blood were smeared on glass slides and fixed immediately in 10% buffered formalin. p21 was examined with avidin-biotin linked immunoperoxidase visualization. Particular attention must be paid to antibody selection and fixation protocol to demonstrate p21, owing to its rapid degradation ex vivo. Three of 16 patients exhibited occasional high p21 expression primarily in leukemic blasts, but in no case were more than 10% of blast cells positive. Normal reticuloendothelial and myeloid cells occasionally exhibited mild to moderately heavy staining, but megakaryocytes, erythroid precursors, lymphocytes and plasma cells were consistently negative. Most patients, 5 normal volunteers and 3 patients with non-malignant disease, exhibited no reactivity, or only a faint blush. These data suggest that while point mutation and concomitant activation of c-N-ras occurs regularly in ANLL, high levels of ras p21 expression are rarely found with this technique.
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PMID:Ras gene product expression in blood and marrow smears of patients with acute leukemia: importance of fixation. 223 1

MCF-7 human breast cancer cells are estrogen dependent for maximal in vitro growth and for tumor formation in nude mice, thus providing a useful model system to study mammary tumorigenesis. A clone of MCF-7 cells transfected with the v-rasH oncogene has been shown to form tumors in the absence of estradiol [Kasid et al., 1985, Science (Wash. DC), 228:725-728]. To extend this observation to more clones of v-rasH-expressing MCF-7 cells and to examine the effects of rasH mutation, we transfected MCF-7 cells with a construct encoding the human c-rasH protooncogene protein product and with three isogenic constructs encoding proteins containing point mutations: arg-12, thr-59, and arg-12 + thr-59 (v-rasH). We isolated several cell lines which produced levels of c-rasH and v-rasH p21 at 30- to 50-fold the levels of controls. We also isolated several cell lines producing the various mutants p21s. All of the transfected cell lines were estrogen-responsive for cell growth. Transfected cells containing high levels of rasH p21 had correspondingly high levels of growth in an anchorage-independent growth assay. Tumorigenesis studies in nude mice, however, showed that some, but not all of the cell lines expressing v-rasH, formed tumors in the absence of estradiol. Tumor formation did not correlate with the level of rasH p21 expression in these cell lines. No tumor formation in the absence of estradiol was observed for cell lines expressing single-mutated or unmutated forms of rasH.
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PMID:Growth properties and tumorigenesis of MCF-7 cells transfected with isogenic mutants of rasH. 240 19

A retrospective analysis was undertaken in which 15 female and 15 male breast cancers were matched by age, stage, estrogen receptor status, and histologic type. Our protocol compares male and female breast cancers for reactivity with antibodies against tumor-associated antigens known to be present on female breast cancer cells. Formalin-fixed sections of each primary tumor were reacted in the ABC immunoperoxidase assay against antibodies B72.3 and DF.3 and an antibody to the ras p21 antigen. Reactivity to B72.3 and DF.3 was similar. However, the ras p21 antigen was expressed to a significantly greater extent in female breast cancers (p = .0008). Thus, although there are similarities in antigenic phenotype of male and female breast cancers, some female breast cancers may have a different pathogenesis as demonstrated by increased amounts of a specific oncogene product.
Breast Cancer Res Treat 1986
PMID:A comparison of tumor-related antigens in male and female breast cancer. 242 26


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