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S Romain

Publications and source records attributed to S Romain.

At least 37 records · Page 2Linked to original sources
PubMed1995

Steroid receptor distribution in 47,892 breast cancers. A collaborative study of 7 European laboratories. The EORTC Receptor Study Group.

Seven laboratories of the EORTC Receptor Study Group reported the distribution of oestrogen (ER) and progesterone receptors (PR) routinely assayed in breast cancer cytosols. A low interlaboratory variability was demonstrated for the median values, and for the frequency of positive tumours as measured by enzyme immunoassay (EIA). Larger variations were found for the frequency of positive tumours, as measured by radioligand binding assay (RLA). They are probably due to differences in the cut-off levels and in the sensitivity of the assay. Analysis of the variability over time clearly demonstrated that the ER-EIA values initially increased compared with RLA. A possible source of variations could be the calibration drift in the ER-EIA kit. In conclusion, quality assessment of steroid receptors should be monitored by comparison of both common standards and distributions routinely obtained in each laboratory. In-house analysis over time is also essential for reagent survey.

Adult↗
PubMed1995

Postnatal depression. Facilitating peer group support.

Health visitors and lay people have been working together in Maidenhead to support women suffering from postnatal illness. Alison Jones, Tricia Watts and Sybil Romain describe how the group supplements medical and psychiatric services, by tackling the isolation women with postnatal depression can feel, and helping them through until the illness ends.

Community Health Nursing↗
PubMed1995

Estrogen and progesterone receptors in breast cancer microsamples simultaneously quantified by enzyme-ligand immunoassay.

A new method (enzyme-ligand immunoassay, ELIA) is described for the estimation of estrogen (ER) and progesterone (PR) receptors in microsamples of human breast cancer tissue. The technique, based on the nonisotopic measurement of receptor-bound estradiol and progesterone, involves three steps: (a) simultaneous saturation of active receptors with their respective authentic ligands, (b) heat treatment of the cytosol to release the steroids from their cognate receptors before or after absorption with dextran-coated charcoal, and (c) measurement of both steroids present in the cytosol by a modified competitive-inhibition enzyme immunoassay. The useful range of the method was 10-4000 pmol/L for ER and 6.5-1000 pmol/L for PR. The correlation coefficient (r) between the one-point and Scatchard plot analysis was 0.95 for ER and 0.99 for PR. Comparison of the one-point ELIA and expected values with the radioligand binding assay (RLBA) results for EORTC samples gave r = 0.88 and 0.99 for ER and PR, respectively. Further comparison of the one-point ELIA with RLBA and with a commercial enzyme immunoassay, in blind testing of cancer tissue microsamples from 70 patients, gave good agreement for ER with r = 0.95-0.97 and concordance of 92.9-94.4% (cutoff, 15 pmol/g protein) against the other two methods. The results were more disperse in all three methods for PR estimation, the assay correlating perhaps better with the enzyme immunoassay (r = 0.90) at a concordance of 89.4% (same cutoff value).

Adult↗
PubMed1995

Comparative study of four extraction procedures for urokinase type plasminogen activator and plasminogen activator inhibitor-1 in breast cancer tissues.

The urokinase type plasminogen activator (u-PA) and the plasminogen activator inhibitor-1 (PAI-1) are among the best second-generation prognostic tissue factors in breast cancer. However, different extraction procedures and assay kits are used in different laboratories. A total of 79 breast tumour tissues stored in liquid nitrogen were analysed in this study. We compared u-PA and PAI-1 levels determined with the American Diagnostics (AD) kit after various extraction procedures. The median cytosolic extraction yield in the presence of 0.4 mol/l KCl, calculated relative to extraction in the presence of 10 ml/l Triton X100 when adapted to standard laboratory working hours (incubation for 2 h instead of 12 h) was 74.4% for u-PA and 85.8% for PAI-1. In addition, the correlations were acceptable. Cytosolic extracts prepared with KCl could permit optimal u-PA and PAI-1 assays while also enabling hormone receptors to be determined with the same specimens. Further studies with clinical data are now necessary to determine the prognostic relevance of this extraction procedure.

Breast Neoplasms↗
PubMed1994

Biological heterogeneity of ER-positive breast cancers in the post-menopausal population.

In the natural history of post-menopausal patients with primary breast cancer, high estrogen receptor levels (ER) have been associated with a poor recurrence-free survival. The purpose of this study was to investigate whether there are any biological intratumoral characteristics to support this puzzling clinical observation. In a population of 542 post-menopausal, primary-breast-cancer patients, 3 normal distributions fitted into the frequency distribution curve of the logarithmically transformed ER-EIA values. The biological profiles of the low ER group, and of the intermediate and high ER groups identified in the ER-positive population were compared. Parameters correlated with ER functional aspect (progesterone receptors and PS2), receptors of epidermal growth factor (EGFR), protease cathepsin D and tumor proliferation (deduced from thymidine kinase activity) were analyzed. As previously reported, the levels of progesterone receptors and PS2 increased significantly from the low to the high ER groups. The highest levels of cathepsin D and thymidine kinase which have been previously related to a poor prognosis in breast cancer were found in the low ER group, but high levels were, surprisingly, also found in the high ER group. This study indicates that the ER-positive post-menopausal population is biologically heterogeneous. The high levels of thymidine kinase found in the high ER group suggest that overexpression of ER may be associated with proliferation enhancement, partly explaining the poor spontaneous prognosis related to this subset.

Breast Neoplasms↗
PubMed1994

Prognostic value of a solubilized fraction of EGF receptors in primary breast cancer using an immunoenzymatic assay--a retrospective study.

In a retrospective study of 319 primary breast cancers, we show that an immunoenzymatic assay of a solubilized fraction of EGF receptors indicates a prognostic value for EGFR which is in contradiction with some (but not all) other studies. It appears that different methodological approaches of measuring EGFR are not equivalent in terms of prognostic power. We emphasize the need for rigorous multicentric standardization and quality control of assays, followed by multistep validation of parameters oriented towards clinical use.

Aged↗
PubMed1994

Acidification reveals a greater number of epidermal growth factor receptors in human placental and breast cancer membranes.

The detection of epidermal growth factor receptors (EGFR) has been proposed as a prognostic factor in different kinds of neoplastic diseases. In this study, we have compared different conditions of EGFR assay, in human placental membranes, in order to establish the best conditions for the routine use of EGFR assay in clinical laboratories. Three kinds of membrane treatment (non-treated, preincubated at 37 degrees C for 30 min, or acid treated at pH 3.0 for 3 min at 0 degrees C), two different separation conditions (hydroxylapatite and centrifugation), two different incubation times (30 min at 37 degrees C and overnight at 18 degrees C) and the effect of proteolytic enzyme inhibitors have been investigated. Preincubated or acid treated membranes showed a two- and three-fold increase of the number of receptors, respectively, as compared with non-treated membranes. In the case of acid pretreated membranes a second, low affinity, site became apparent. Both separation methods gave similar results. The addition of aprotinin had an effect only during long incubation conditions. Freezing of membranes in liquid nitrogen, followed by storage at -80 degrees C for 48 h, resulted in three different patterns. No change was observed in non-treated membranes. Preincubated samples showed a significant decrease both in the number and the affinity of detected EGFR. Acid treated membranes showed a decrease of the affinity of high affinity EGFR with no modification of their number. It is proposed that acid pretreatment, freshly prepared membranes, addition of aprotinin and the use of hydroxylapatite, for the separation of bound and free radiolabelled EGF, should be used in order to standardize the EGFR assay in clinical laboratories. Using these conditions, we were able to detect a significantly higher number of EGFR in 6/29 cases of human breast cancer specimens.

Breast Neoplasms↗
PubMed1994

Technical evaluation of thymidine kinase assay in cytosols from breast cancers. EORTC Receptor Study Group Report.

Pilot retrospective studies have pointed to the prognostic value of thymidine kinase (TK) in breast cancer. We studied the Prolifigen TK-REA assay (Sangtec Medical, Sweden), usually applied to serum, for TK analysis in breast cancer cytosols. Reproducibility was good, provided that small volume pipetting was performed carefully. The TK assay was not influenced by the short-term storage of cytosols in liquid nitrogen or at -80 degrees C. However, some steps appeared critical for good laboratory practice. The TK level was affected by thawing the cytosols more than twice. Tumour storage in liquid nitrogen should be preferred over storage at -80 degrees C. The components of the homogenisation buffer, especially sodium molybdate and KCl can have a marked influence on results. Finally, linearity problems arose with some cytosols. Thus, although assay of TK in cytosols is apparently simple, care must be taken in practice. The TK-REA kit should be standardised before widespread use in breast cancer.

Breast Neoplasms↗
PubMed1994

Determination of oestrogen receptors by enzyme immunoassay. Technical differences between laboratories and their consequences.

When multicentre breast cancer trials are performed, receptor analyses must be comparable both over time and in the participating laboratories. However, we show for the first time a high variability for the distribution of oestradiol receptor (ER) values measured by enzyme immunoassay (EIA) from 1987 to 1991. This variability could be explained by calibration changes in the immunoassay kits. We have also analysed the influence on ER-EIA levels of technical differences between laboratories apart from the assay itself. Many steps emerged as being critical, i.e. homogenisation buffer, homogenisation procedure and cytosol dilution. Finally, we show that addition of 4-monohydroxytamoxifen increases the apparent ER content measured by EIA in 92% of cytosols. Thus, many factors must be controlled to ensure high precision with ER-EIA assays. We have to be particularly cautious with the conformational changes that could occur during cytosol preparation and that could also pre-exist in the tumour samples. Quality controls of cytosol preparation are essential.

Breast Neoplasms↗
PubMed1994

Prognostic value of cytosolic tyrosine kinase activity in 249 node-positive breast cancer patients.

Tyrosine-specific protein kinase (TPK) has been associated with the cytoplasmic domain of growth factor receptors as well as oncoproteins. Enzymatic activation appears to be a major initial event in these signal transduction pathways. In this study, TPK was determined in the cytosols of 249 node-positive primary breast tumours. Enzyme activity was measured using [32P]ATP and poly(glutamic acid-tyrosine) (4:1) as an artificial substrate. Levels of TPK varied from 0 to 35.9 pmol ATP min-1 mg-1 protein (median 11.4). No correlation was found with tumour size or number of positive lymph nodes. In contrast, levels of TPK were negatively associated with age (P = 0.01) and menopausal status (P < 0.05) of the patients. Higher concentrations of TPK were in addition found in tumours negative for oestradiol (P < 0.01) and progesterone (P < 0.05) receptors. Finally, a positive correlation was found between TPK and urokinase plasminogen activator (UPA) (P < 0.05). Patients whose tumours contained high levels of TPK had reduced disease-free (P = 0.01) and overall survival (P < 0.05). In Cox multivariate analysis, including patient's age, menopausal status, tumour size, number of positive lymph nodes, steroid receptors and UPA, TPK retained its independent prognostic importance.

Adult↗
PubMed1994

Biochemical and immunohistochemical multiparametric analysis of steroid receptors and growth factor receptors in human normal endometrium in spontaneous cycles and after the induction of ovulation.

This study was carried out with three aims: to assess the variations of receptors for beta-oestradiol and progesterone, and for epidermal growth factor (EGF), alpha-fibroblast growth factor (FGF) and beta-FGF, during a spontaneous cycle in normo-ovulatory patients, 2 days before, and 2 and 7 days after the day of ovulation; to compare the control group of patients with those given ovulation induction using a multiparametric approach; and to study the role of luteal supplementation with progesterone in two groups of patients treated by a luteinizing hormone-releasing hormone agonist plus human menopausal gonadotrophin. The results were assessed by biochemical analyses and by immunohistochemistry. In spontaneous cycles, a decrease in steroid receptors occurred during the luteal phase. There was an increase in EGF and EGF receptors which was induced by oestradiol secretion, and an increase during the luteal phase of alpha-FGF and beta-FGF, which are considered to be angiogenic factors. Comparisons between spontaneous and induced cycles showed a few variations in the endometrium but no differences were related to the type of ovulation induction.

Adult↗
PubMed1994

Prognostic significance of autoantibodies to laminin in the sera of breast cancer patients: a preliminary report.

Interactions between cancer cells and laminin play an important role in the metastatic cascade. The aim of this retrospective study was to evaluate the presence and the prognostic significance of autoantibodies to laminin in sera of patients with breast cancer. Our study population consisted of 71 high-risk primary breast cancer patients (median follow-up, 6 years). IgG, IgA and IgM were analysed at the time of surgery and before any treatment was given. Concentrations were measured by enzyme immunoassay with a highly purified antigen. IgG, IgA and IgM anti-laminin median values were, respectively 117%, 130% and 97% of normal absorbance. Higher concentrations of IgM to laminin were found in pre-menopausal patients as compared with post-menopausal patients (p < 0.001). Patients with high concentrations of IgG to laminin had lower disease-free (p = 0.003) and overall survival rates (p = 0.003). In breast cancer, assay of IgG to laminin could thus provide a cheap and easy prognostic index available for all patients.

Adult↗
PubMed1994

[Intra-tissue biological markers in cancers of the breast: current assessment].

Among the great many prognostic factors currently available in breast cancer, three classes of tissue biological parameters appear to be the most reliable in the establishment of a clinical decision flowchart, when they will have been technically and clinically validated: parameters of hormone dependence, tumour aggressiveness and invasion and parameters of proliferation. This article discusses the difficulties encountered in the evaluation of some of these parameters (hormone receptors by various methodological approaches, proteases, enzymes involved in cell proliferation), with emphasis on standardisation of techniques, development of quality controls, clinical validation and objective information of the medical and scientific communities.

Biomarkers↗
PubMed1992

Multiparametric prognostic evaluation of biological factors in primary breast cancer.

BACKGROUND: An array of biological features related to tumor cell differentiation status, growth rate, and invasive potential have been identified as potential prognostic factors in breast cancer. We were interested in determining their relative importance in predicting patient survival. PURPOSE: We evaluated the relative weight of the following four biological factors in predicting survival of patients with breast cancer: tumor cell DNA content (determined by flow cytometry), tumor cell proliferation rate (determined by thymidine kinase activity), expression levels of cathepsin D and urokinase plasminogen activator, and several "classical" clinical and histological factors. METHODS: Selected from a prospectively updated database, the study population consisted of 319 primary breast cancer patients who received treatment and follow-up care (median, 6 years) in the Centre René Huguenin. To determine the profile of biological factors for each patient, we used frozen tumor specimens and (except for the flow cytometric DNA content assay) commercially available assay kits. We determined by Cox multivariate analysis the relationships of the biological factors to each other, to classical prognostic factors, and to disease-free and metastasis-free survival. RESULTS: In the overall population, disease-free survival was best predicted by node status (P = .004), clinical tumor size (P = .02), and cathepsin D expression (P = .01), whereas metastasis-free survival was best predicted by node status (P = .0004), clinical tumor size (P = .009), and urokinase plasminogen activator expression (P = .04). In node-negative patients, thymidine kinase activity was the only factor selected for disease-free (P = .04) and metastasis-free (P = .05) survival. In node-positive patients, the number of positive axillary lymph nodes was the only factor selected for disease-free (P = .0008) and metastasis-free (P = .00017) survival. CONCLUSIONS: Our retrospective analysis has identified protease expression and tumor cell proliferation rate as important biological prognostic factors in breast cancer. Prospective clinical trials should be undertaken to confirm these results.

Adult↗
PubMed1992

c-myc gene amplification in selected node-negative breast cancer patients correlates with high rate of early relapse.

In breast cancers with histologically negative axillary nodes selected for high frequency of recurrence, the amplification of c-myc, erbB-2 and int-2 genes was found to concern, respectively 25% (16/65), 31% (25/81) and 14% (10/70) of tumours. Their relation with tumour progression expressed by relapse-free survival is reported. Using univariate analyses, c-myc amplified tumours showed significant association with early (30-month period after diagnosis) (P = 0.0013) and intermediate (50-month period after diagnosis) (P = 0.0398) risks of recurrence. In contrast, only a trend towards higher relapse was observed in erbB-2 amplified breast cancers with respect to later events (occurring over the first 30-month period). Multivariate analyses indicated that c-myc amplification is an independent prognostic factor stronger than oestrogen receptor status and tumour size to define a high risk subset in node-negative patients selected for high frequency of recurrence.

Adult↗
PubMed1992

Inflammatory carcinoma of the breast.

Inflammatory breast carcinoma has to be defined by accurate clinical and pathological criteria. The prognosis is very poor and improvements made by chemotherapy are limited to the increase in the disease-free period and overall survival for a few months.

Adult↗