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Biomedical subjects

S Nicholson

Publications and source records attributed to S Nicholson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.

Sections of formalin-fixed, paraffin-embedded tissue from 185 primary breast carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining, which is known to correlate with gene amplification, was associated with earlier relapse, shorter postrelapse survival, and shorter overall survival. Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. Expression of the c-erbB-2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer.

Analysis of Variance↗
PubMed1989

Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer.

Epidermal growth factor receptors (EGFR) and oestrogen receptors (ER) were analysed in 221 patients with primary operable breast cancer by means of radioligand assays. After median follow-up of 24 months (range 3-60 months), there had been recurrences in 99 patients, of whom 72 (median age 56 years, range 32-77 years) received tamoxifen alone as first-line treatment for recurrence. 20 patients (28%) showed a response to this therapy and 52 (72%) did not. Of 32 ER-positive tumours, 12 (37.5%) showed an objective response to tamoxifen compared with only 2 of 40 (5%) ER-negative tumours (p less than 0.005). Of 35 EGFR-positive tumours, 3 (8.5%) achieved an objective response compared with 11 of 37 (30%) EGFR-negative tumours (p less than 0.05). Only 1 of 28 EGFR-positive, ER-negative tumours achieved an objective response. Including patients whose disease remained stable for more than 6 months with the responders, however, EGFR status was a better predictor of response to tamoxifen; 15 of 37 EGFR-negative patients and 5 of 35 EGFR-positive patients responded (p less than 0.01), compared with 13 of 32 ER-positive and 7 of 40 ER-negative patients (not significant). EGFR expression is a highly significant marker of poor prognosis in patients with breast cancer; it appears to be as good a predictor as ER for objective response and better for overall response to endocrine therapy on relapse.

Adult↗
PubMed1989

Epidermal growth factor receptors in breast cancer: association with early relapse and death, poor response to hormones and interactions with neu.

Epidermal growth factor receptors (EGFRs) were measured in 221 primary breast cancers by ligand binding with 125I-labelled EGF, and high-affinity sites were quantitated. There was a highly significant inverse relationship between oestrogen receptor (ER) and EGFR (15 EGFR-positive [EGFR+]ER+ and 92 EGFR-negative [EGFR-]ER+: 54 EGFR- ER- and 60 EGFR+ ER-). The relapse-free survival and overall survival were significantly shorter for EGFR+ vs EGFR- tumours (P less than 0.001) by about 2 yr in the case of relapse-free survival. When ER- tumours were substratified by EGFR status, the EGFR- ER- tumours had a prognosis almost as good as the ER+ tumours. In 31 of 184 cases, high expression of neu, correlating with amplification, was found. Expression of neu conferred similar poor prognosis to EGFR expression in all prognostic subgroups. Coexpression of neu and EGFR had an additive adverse effect. Epidermal growth factor receptors (EGFR) and oestrogen receptors (ER) were analysed in 221 patients with primary operable breast cancer by means of radioligand assays. After median follow-up of 24 months (range 3-60 months), there had been recurrences in 99 patients, of whom 72 (median age 56 yr, range 32-77 yr) received tamoxifen alone as first-line treatment for recurrence. 14 patients (19%) showed a response to this therapy and 58 (81%) did not. Of 32 ER+ tumours, 12 (37.5%) showed an objective response to tamoxifen compared with only 2 of 40 (5%) ER- tumours (P less than 0.005). Of 35 EGFR+ tumours, 3 (8.5%) achieved an objective response compared with 11 of 36 (30%) EGFR tumours (P less than 0.05). Only 1 of 28 EGFR+, ER- tumours achieved an objective response. Including patients whose disease remained stable for more than 6 months with the responders, however, EGFR status was a better predictor of response to tamoxifen; 15 of 37 EGFR- patients and 5 of 35 EGFR+ patients responded (P less than 0.01).

Adult↗
PubMed1989

Duplex ultrasonography of the fetal aorta, umbilical artery, and placental arcuate artery throughout normal human pregnancy.

A cross-sectional duplex study of blood flow in the fetal aorta, umbilical artery, and arcuate arteries of 111 normal subjects was performed once at between 20 and 42 weeks gestation. Peak systolic velocity, end-diastolic velocity, mean velocity, and volume flow were measured in the fetal aorta, and systolic to diastolic (S/D) ratios were measured in all three vessels. Velocities show an inverse exponential (Y = Exp [1/X x B + C]) increase with gestational age, reaching a plateau just before term, while S/D ratios in the aorta and umbilical arteries show a linear decrease. Such findings are at variance with some published data. Our results suggest a reduction in fetal placental resistance at term and provide useful data concerning normal fetal and placental circulations.

Aorta↗
PubMed1988

Relationship of membrane-bound tissue type and urokinase type plasminogen activators in human breast cancers to estrogen and epidermal growth factor receptors.

The total plasminogen activator (PA) activity and the activities of urokinase type (uPA) and tissue type (tPA) plasminogen activators were measured in 43 primary human breast cancer homogenates. The majority of the PA activity was found in the 100,000 X g crude membrane pellets (log mean of 490 milli-IU/mg of protein, +1169, -346), and little PA activity was present in the cytosolic supernatant (log mean of 19 milli-IU/mg of protein, +168, -17). The activities of total PA and of each type of PA were compared to the estrogen receptor (ER) and epidermal growth factor receptor (EGFR) status of the tumors and to their histological grade. Total PA activity and uPA activity were not significantly different in any group of tumors stratified according to receptor status or tumor grade. Tissue type PA levels, however, were significantly lower in ER-negative compared with ER-positive tumors and in EGFR-positive compared with EGFR-negative tumors (P less than 0.01 and less than 0.05, respectively). The tPA activity was also related to grade, decreasing with worsening differentiation (P = 0.04). The ER-negative tumors were further stratified into EGFR-positive and -negative subgroups. Only the ER-negative tumors possessing EGFR had significantly lower tPA levels than the ER-positive tumors (P less than 0.01). Low tPA levels in breast cancers were, therefore, associated with ER negativity combined with EGFR positivity and may be an indication of poorer differentiation and prognosis.

Breast Neoplasms↗
PubMed1988

Quantitative assays of epidermal growth factor receptor in human breast cancer: cut-off points of clinical relevance.

Epidermal growth factor receptor (EGFr) assays were performed by 3 different methods on 246 human primary breast carcinomas. Scatchard analyses of multipoint binding data on 19 of the first 209 tumours, performed by a displacement method, demonstrated that the majority of tumours exhibited 2 classes of binding site, the high-affinity site with an affinity constant (KD) of mean 2 nmol/l (SD 1.3, range 0.44-7 nmol/l), and a low-affinity site, KD mean 9.5 nmol/l (range 6-15.5 nmol/l). Scatchard analysis of multipoint assays using increasing concentrations of 125I-labelled EGF showed that saturation of the high-affinity site occurred in the majority of saturation of the high-affinity site occurred in the majority of tumours at a concentration of labelled EGF of I nM. Comparison of the KD values of the high-affinity site obtained from displacement assays with those obtained by increasing labelled EGF showed that the KD was significantly higher (p = 0.0002) when measured by the latter method. There was no difference in binding capacity of the high-affinity or low-affinity sites by the 2 methods. A 2-point assay with I nM labelled EGF (specific activity approx. 80-130 microCi/microgram) correlated with quantitative values for the high-affinity site from Scatchard analysis (p less than 0.02). There was a strong inverse relationship between EGFr greater than 10 fmol/mg membrane protein (2-point assay) and ER (dextran-coated charcoal method), Chi-squared 2 X 2 contingency table test = 34.027, p less than 0.0001. Follow-up data from 135 patients revealed a strong inverse relationship between EGFr greater than 10 fmol/mg membrane protein and oestrogen receptor (ER) status and a positive correlation with early recurrence and death. Our data describe a reproducible assay for EGFr and show that a cut-off point at 10 fmol/mg allows clinically useful application.

Binding Sites↗
PubMed1988

Use of fine needle aspiration cytology with immediate reporting in the diagnosis of breast disease.

Fine needle aspiration biopsy for cytological examination (FNAC) is becoming increasingly accepted as a means of tissue diagnosis in breast disease. This study examines the feasibility and accuracy of FNAC in 'immediate reporting' by a consultant cytopathologist in a busy breast clinic. Over a 2-year period, 884 cytology reports were analysed. An initial clinical report and subsequent final cytological diagnosis was made. Fine needle aspiration provided adequate material for cytological evaluation in 635 of the 884 biopsies (71.6 per cent) and this proportion was greater when discrete lumps were considered (463 of 562 biopsies = 82.4 per cent). In diffuse and cystic disease, however, the adequacy of specimens was reduced: 50 per cent and 65 per cent respectively. On immediate reporting the diagnostic sensitivity for all patients was 88 per cent (discrete lumps only, 92.5 per cent) and the specificity was 99.8 per cent (discrete lumps only, 100 per cent). FNAC retains its diagnostic accuracy when immediate reporting is employed and this study demonstrates that this technique can be used in making a diagnosis in patients with breast disease.

Biopsy, Needle↗
PubMed1988

Natural history of the benign breast lump.

A prospective study of 112 patients with clinically discrete benign breast lumps has shown that 68 per cent of patients experienced resolution of their lumps over a period of up to 2 years. Resolution of both fibro-adenomas and discrete areas of fibro-adenosis was observed. Diagnosis was achieved by clinical examination and fine needle aspiration cytology. Four patients thought clinically to have benign disease were proven by cytology to have a carcinoma, but no patient with a cytopathological diagnosis of benign disease has developed cancer during or subsequent to this study. We recommend that patients under 35 years of age with clinically and cytologically benign breast lumps can be offered the option of non-excision in the reasonable expectation of resolution of their lesion.

Adenofibroma↗
PubMed1988

Relationships between oestrogen receptor,epidermal growth factor receptor, ER-D5, and P24 oestrogen regulated protein in human breast cancer.

Proteins regulated by or related to the oestrogen receptor (ER) may prove to be more reliable indicators of prognosis and hormone sensitivity then expression of the receptor itself. It has been shown recently that expression of epidermal growth factor receptor (EGFR) is associated with a poor prognosis in breast cancer. In a series of 60 breast cancers, we have studied relationships between ER, ER-D5 oestrogen receptor related protein, P24 oestrogen regulated protein, and EGFR using an immunohistochemical technique employing monoclonal antibodies in each case. In addition, radioligand binding assays for ER and EGFR were carried out and tumour histological grade was determined. Seventy-one per cent and forty-three per cent of tumours stained for ER-D5 and P24, respectively, but there was no relationship between staining for these and ER or EGFR status. There was a significant correlation between staining for ER and EGFR, and the respective biochemical assays. Relating ER to EGFR, very few ER-positive cases expressed EGFR, but this relationship fell short of significance. The prognostic significance of expression of the epitopes recognized by the ERD5 and P24 antibodies must await assessment of clinical outcome.

Antibodies, Monoclonal↗
PubMed1988

Pulmonary hypoplasia testing in clinical obstetrics.

An ultrasound-based diagnostic test for predicting pulmonary hypoplasia antenatally by measurements of fetal chest circumference was applied prospectively to 45 patients at risk for developing this disorder. The outcome for the newborn infant and the autopsy findings were correlated with the antenatal prediction. The results of this test demonstrated a sensitivity and a specificity of 88% and 96%, respectively. The application of this test to clinical practice is recommended.

Amniotic Fluid↗
PubMed1988

Evaluation of fetal cardiac dysrhythmias with two-dimensional, M-mode, and pulsed Doppler ultrasonography.

Forty-three patients with fetal cardiac dysrhythmia were referred to a tertiary ultrasound department for further evaluation. The patients were subdivided according to the type of dysrhythmia diagnosed. All patients with irregular fetal heart rate had a good perinatal outcome. Of the six patients with fetal tachycardia, two required in utero therapy with maternal digoxin, and one of these fetuses had a cardiac tumor. The eleven patients with fetal bradycardia had the worst perinatal outcome, with four deaths occurring. The results suggest that all patients with fetal tachycardia or bradycardia should have a complete fetal cardiac assessment in a center experienced with the management of such cases.

Algorithms↗
PubMed1988

Atrial natriuretic peptide production in association with nonimmune fetal hydrops.

The presence and elevation of atrial natriuretic peptide in fetuses has not previously been demonstrated. This study of right atrial pacing in fetal lambs demonstrated a threefold to fourfold increase in atrial natriuretic peptide during the production of fetal hydrops. Its rate of return to a normal level paralleled the clearance of fetal hydrops. Its possible role in fetal cardiovascular hemodynamics is discussed.

Animals↗
PubMed1988

Epidermal growth factor receptor status of histological sub-types of breast cancer.

The histological breakdown of a consecutive series of 264 surgically resected malignant lesions of the breast was studied. Oestrogen and epidermal growth factor receptor status was quantified and presented along with size and lymph node status of the non-ductal lesions. Those non-ductal tumours containing EGF receptors have all recurred within two years of resection. Twenty-one percent of the lobular carcinomas contained EGF receptors compared to 34% of ductal carcinomas. EGF receptor status appeared to be associated with an increased risk of early recurrence and death whatever the histological sub-type of the breast cancer.

Breast Neoplasms↗
PubMed1988

Measurement of oestrogen receptor mRNA levels in human breast tumours.

A sensitive single-stranded hybridisation probe for the oestrogen receptor mRNA was synthesised using T3 polymerase from oestrogen receptor cDNA cloned in the Bluescript vector. This probe was used to measure oestrogen receptor mRNA in total RNA extracted from breast tumours. Oestrogen receptor mRNA was detected in 41 of 47 (87%) tumours whereas cytosolic oestrogen receptor protein was detected in only 18 out of 39 (46%). There was a significant correlation between the levels of the oestrogen receptor, as measured by 3H-oestradiol binding, and the oestrogen receptor mRNA. Oestrogen receptor mRNA was detected in 15 of the 21 tumours that did not contain detectable oestrogen receptor protein. This suggests that detection of the mRNA is a more sensitive means for establishing oestrogen receptor status than the radioligand oestrogen receptor assay. Oestrogen receptor mRNA was found in all histological tumour types examined. Its level was related to tumour differentiation. All the tumours that did not contain oestrogen receptor mRNA and most of the tumours that contained only low levels of oestrogen receptor mRNA were classified as grade III according to Bloom and Richardson: the median of the oestrogen receptor mRNA levels was significantly lower in this group.

Adult↗
PubMed1988

Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients with breast cancer.

We have used primary endocrine therapy for 61 elderly women with operable breast cancer (median age 77 years). Eleven patients (18%) had complete and 24 (39%) partial tumour regression, 12 (20%) had stable disease for a minimum of six months and 14 (23%) no response. Salvage surgery was undertaken in the 14 with no response and 8/9 with progressive disease following initial response, thus samples were available from relapse patients only. Assays for EGFr (two point radioreceptor assay) and oestrogen receptors (ER) (dextran coated charcoal method and an immunohistochemical method) were performed on 20/22 patients. Ten of these 20 tumours were EGFr+ (greater than 10 fmol mg-1 binding) and 9/13 patients progressing within six months had EGFr+ tumours. 15/22 were available for ER evaluation and there was no such association with ER status. EGFr status was also associated with early recurrence after surgery and death in the endocrine failure group (P less than 0.005 and P less than 0.05 respectively). Of a control population of 33 patients (median age 72 years) treated by primary surgery, only 6 were EGFr+. In this group early relapse was predicted by EGFr status, but not by ER status (median disease free survival for EGFr+ patients 15 months, and for EGFr- patients 40 months, P less than 0.01, logrank test). There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P less than 0.001). EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions.

Aged↗