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)

Using intact ethanol-fixed cytokeratin monoclonal (CAM 5.2) and propidium iodide dual-stained cells, we have performed two-color multiparametric flow cytometric (FCM) DNA analysis and S-phase fraction (SPF) determination on 165 mechanically dissociated breast carcinomas. Sixty-seven patients were axillary node positive, 33 patients node negative; 59 had biopsy only and in 8, FCM was performed on tissue from metastatic lesions. Overall, 62% of the tumors contained aneuploid cell populations. Abnormal cellular DNA content (aneuploidy) was significantly correlated with high nuclear grade (p less than 0.001), lack of estrogen receptors (p less than 0.001), presence of vascular invasion (p less than 0.04), high histologic grade (p less than 0.04), and tumor size (p less than 0.03) but not with patient age (p greater than 0.07) or axillary node status (p greater than 0.50). SPF values derived from ungated histograms had a positively skewed frequency distribution (range 2 to 30%, N = 152) with an overall median of 11% (diploid, 8.9%; aneuploid, 15.7%). Higher SPF values were significantly correlated with aneuploidy (p less than 0.001), presence of necrosis (p less than 0.001), lack of estrogen receptor (p less than 0.0001), high nuclear grade (p less than 0.001), vascular invasion (p less than 0.003), tumor size (p less than 0.006), and high histologic grade (p less than .004) but not the presence of lymph node metastases (p greater than 0.56). Mean SPF values were significantly higher when calculated from cytokeratin gated DNA histograms (14.1% versus 11.5%, p less than 0.001), probably due to exclusion of contaminating stromal/inflammatory cells; and significantly lower when calculated from debris subtracted histograms (7.8% versus 11.4%). Cytokeratin gated and debris subtracted SPF values both had a greater degree of correlation than ungated values with clinicopathologic factors of known prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry. Clinicopathologic correlations. 169 Mar 16

An immunocytochemical assay using a monoclonal antibody specific for estrogen receptor (ER-ICA) was performed on needle aspirates and on histologic sections (mastectomy and biopsy specimens) from 55 patients with breast cancer. A total of 82 ER-ICAs were performed, with matched cytologic and histologic specimens in 27 patients, cytology alone in 15, and histology alone in 13. ER-ICA results were described by a histochemical score (H score) based on intensity-weighted percentages of staining cells. The H scores were compared with results of sucrose density gradient (SDG) analysis of histologic specimens (mastectomy, resection, or biopsy). An H score greater than or equal to 10 and an SDG value greater than or equal to 10 fmol/mg protein were considered positive. The sensitivity of cytologic ER-ICA was 94%, the specificity 100%. The sensitivity of histologic ER-ICA was 67%, the specificity 90%. Correlating cytologic H score with Black's nuclear grade showed that grade 1 (the most anaplastic) carcinomas demonstrated the lowest H scores (mean, 7.3 +/- 29.8), whereas the highest H scores were noted in grade 3 tumors (mean, 150.0 +/- 88.1). Both SDG and ER-ICA showed ER values to be lower in premenopausal than postmenopausal women. There was no correlation between H score and presence of axillary nodal metastases or tumor size. An overall good correlation was demonstrated between immunohistochemical methods and biochemical analysis.
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PMID:Comparison of immunocytochemical and biochemical assays for estrogen receptor in fine needle aspirates and histologic sections from breast carcinomas. 169 28

The role of radical axillary dissection in breast cancer management is presently under discussion. In this study we have evaluated the relationship between the pattern of metastatic axillary lymph node involvement by level and some of the main prognostic factors (age of the patient, size, grading, estrogen receptor and progesterone receptor status of the primary tumor) in 185 patients with operable breast cancer. The III level appeared to be involved in 31 (16.8%) out the 108 patients with axillary lymph nodes positive for metastases. A discontinuous pattern of axillary involvement (skip metastases) was observed in about 10% of cases. Logistic regression analysis of the data shows that only G3 is significantly correlated with the risk of III level invasion (p less than 0.05). We conclude that, at present, a selection of possible candidates for a less than radical axillary dissection is not as yet feasible. Since the risk for III level invasion cannot be sufficiently defined.
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PMID:Predictive value of some clinical and pathological parameters on upper level axillary lymph node involvement in breast cancer. 174 1

Radioestrogens have potential as adjunct therapeutic agents against ovarian carcinoma, because selected radionuclides can deposit lethal doses of radiation to tumor cells and many ovarian carcinomas and their metastases express estrogen receptors. Because intraperitoneal administration is a possible approach, we investigated absorption from the peritoneal cavity of a radioiodoestradiol after intraperitoneal application in rats with and without ovarian tumors and ascites and compared the distribution of the radioactivity with that obtained after intravenous injection. In the absence of ascites, 70% of the intraperitoneal dose was cleared into the intestine within 2 hours after injection, indicating fast absorption from the peritoneal cavity. In the presence of ascites, clearance of intraperitoneal radioiodoestradiol was considerably slower; at 2 hours after injection, 50% of the injected dose remained in the ascites, mostly as radioiodoestradiol. Uptake of radioactivity in estrogen receptor-rich tissues, e.g., uterus, after intraperitoneal injection was high (about 20:1 over blood), regardless of the presence of ascites, but moderately lower than that observed after intravenous injection of radioiodoestradiol.
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PMID:Prolonged clearance of intraperitoneal 16 alpha-[125I]iodo-17 beta-estradiol in presence of ascites. 175 Apr 85

The capacity of steroidal regulatory influence on benign and malignant mammary tissue in cats was investigated. Estrogen, progestin, and (in some cats) androgen receptor levels in the cytosol were measured by a multiconcentration dextran-coated charcoal method in non-affected mammary tissue (NAMT) and in benign and malignant mammary lesions from 34 cats. Receptor levels less than 5 fmol/mg protein were considered negative. Since 3 out of 4 NAMT samples had low-positive estrogen receptor and progestin receptor levels, we considered specimens in which tumour cells were intermeshed with NAMT separate from "pure" tumour specimens. The variation in estrogen receptor expression between the different tissues was moderate, there being 9/17 malignant lesions (without NAMT) estrogen receptor+ as compared with 6/6 benign lesions (without NAMT) (p less than 0.05). The variation in progestin receptor expression was greater (p less than 0.02), with only 5/17 malignant lesions-(without NAMT) progestin receptor+ as compared with 6/6 benign lesions (without NAMT). The difference in progestin receptor levels between these 2 groups was also statistically significant. In 5 cats metastases were also assayed and 2 had a low-positive estrogen receptor level, whereas 1 had a low-positive progestin receptor level. Two of 9 malignant lesions (without NAMT) had positive androgen receptor levels. Comparison of the steroid receptor expression of human and feline mammary cancer indicates that estrogen receptor and progestin receptor levels are lower in the latter. This may indicate that loss of steroid hormone dependency occurs at an earlier stage of the disease in feline mammary cancer than in human breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Steroid receptors in mammary tumours of the cat. 180 1

A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.
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PMID:Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The Breast Cancer Study Group. 185 77

Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer.
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PMID:The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. 185 86

The estrogen receptor (ER) status is an important factor for prognosis and endocrine therapy of breast cancer. Therefore 16-alpha-123I-iodoestradiol-17-beta (123I-E2) as a receptor-specific radiopharmacon was used for scintigraphic tumor detection in 62 patients suspected of breast cancer. The studies were performed as a multicenter trial (5 university hospitals) to validate the method and to overcome methodical problems. A fast tracer elimination from the blood pool into the liver was seen, followed by biliary excretion allowing early imaging of the thorax due to low background activity but resulting in difficult imaging conditions of the abdomen. In 42 patients (30 carcinomas, 12 benign lesions) the overall sensitivity was 66% (ER status cut-off: 10 fmol/mg). Some patients with breast cancer showed focal or diffuse uptake in the area of primary lymph drainage (parasternal, axillary) without any clinical correlation, demanding follow-up investigations. There was only one false-positive result in a receptor-negative primary carcinoma; thus, the non-invasive determination of the ER status seems to be feasible. The sensitivity of 123I-E2 in the detection of primary breast cancer or metastases and recurrences is low compared to mammography and other methods; therefore, 123I-E2 scintigraphy cannot be used as a screening method. Differentiation of malignant and benign tissue is even more difficult as both may have a positive ER status, for example in mastopathy. Nevertheless, 123I-E2 scintigraphy is an in vivo imaging technique for the detection of breast cancer depending on the ER status and provides information about tumor localisation. It may become a specific method for the non-invasive diagnosis of the ER status and may be helpful in follow-up studies. As a receptor-specific agent 123I-E2 may give answers to questions of tumor heterogeneity and changes of the ER status during therapy.
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PMID:[Tumor scintigraphy using 123I-labeled estradiol in breast cancer--receptor scintigraphy]. 187 Oct 7

Breast cancer is a common primary malignancy in women. On rare occasion the breast is also the site of metastatic disease. This report describes the evaluation of breast and axillary masses in a patient with known ovarian cancer, including the radiographic evaluation and special immunohistochemical stains with CA-125. Flow cytometric determinations and hormonal receptor analysis on both the primary and metastatic tumors demonstrate similar biologic characteristics. Both tumor sites demonstrated positive CA-125 staining, aneuploid DNA populations, moderately positive estrogen receptor content, and negative progesterone receptors. The mammogram demonstrated a well-circumscribed lesion with several areas of microcalcifications. Blood-borne metastasis from the ovary to the breast can show a varied clinical picture that can be differentiated from that of a primary breast carcinoma.
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PMID:Ovarian carcinoma metastatic to the breast and axillary node. 188 82

We have studied the estradiol sensitivity of primary human breast carcinomas in organ culture in a prospective pilot series of 109 tumors. The effect on plasminogen activator (PA) production was used as the end-point of estrogen action. We found that: (i) All tumors secreted detectable levels of urokinase-type PA (uPA); the level of basal uPA production was markedly heterogeneous but showed a weak association with the level of estrogen receptor positivity (p = 0.049). (ii) Only 23.5% of the tumors secreted tissue-type PA (tPA) in addition to uPA; a higher proportion of these tumors had histological characteristics indicative of good prognosis (18% vs. 3% of tumors secreting only uPA). (iii) Estradiol modulated uPA production and this effect was receptor-mediated. (iv) Responsiveness to estradiol was limited to a subset (25 of 60 or 41.7%) of estrogen and progesterone-receptor-positive tumors. (v) Of 20 evaluable patients with lymph-node and receptor-positive breast cancer who received adjuvant anti-estrogen therapy, 11 were identified as estradiol-sensitive by the in vitro PA assay; of these, 10 had no evidence of disease after a median follow-up period of 3+ years. In contrast, of 9 patients with tumors identified as estradiol-insensitive, 4 developed metastases within 3+ years of follow-up. (vi) Consistent with the previously reported inhibitory effect of corticosteroids on uPA production in organ cultures of human tumors, the basal culture level of uPA produced by tumors from patients receiving corticosteroids at the time of surgery was significantly lower than the level of uPA in the remaining tumors (p = 0.029). Also, tumors from patients receiving thyroid hormone, known to stimulate uPA in vitro, showed a slight trend toward increased production of uPA. These results show that hormone effects on tumor PA production are qualitatively similar in organ culture and in the host. This and the emerging individual correlation between sensitivity to estradiol in vitro, as determined by PA, and the clinical effectiveness of anti-estrogen therapy, underscore the potential usefulness of the organ culture approach.
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PMID:Estradiol modulation of plasminogen activator production in organ cultures of human breast carcinomas: correlation with clinical outcome of anti-estrogen therapy. 190 Dec 98


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