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B Angus

Publications and source records attributed to B Angus.

122 records · Page 7Linked to original sources

Prognostic factors in breast cancer: immunohistochemical staining for SP1 and NCRC 11 related to survival, tumour epidermal growth factor receptor and oestrogen receptor status.

It has been proposed that intense immunohistochemical staining using the monoclonal antibody NCRC 11 is indicative of a better prognosis in breast cancer, and that expression of pregnancy specific glycoprotein (SP1) and epidermal growth factor receptors (EGFR) are poor prognosis indicators. In order to evaluate the significance of staining for NCRC 11 to prognosis and to these other variables, we studied two series of breast cancer patients. In one series (n = 93), staining with NCRC 11 and for SP1 was correlated with prognosis: in neither case was there any overall relationship between staining and survival. However, when the patients were stratified by tumour histological (Bloom's) grade, SP1 expression was associated with a poorer prognosis in grade II tumours (p less than 0.025). In a further series (n = 94), NCRC 11 staining was carried out and fresh tumour samples were assayed biochemically for oestrogen receptor (OER) and EGFR. NCRC 11 showed a negative correlation with EGFR status (p = less than 0.05) but no significant association with OER status. Thus despite our demonstration of a negative correlation with an indicator of poorer prognosis, we were unable to demonstrate any direct relationship between staining with NCRC 11 and survival.

Antibodies, Monoclonal↗

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue.

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.

Antibodies, Monoclonal↗

Practical value of genotypic analysis for diagnosing lymphoproliferative disorders.

The value of DNA hybridisation (using immunoglobulin and T cell receptor gene probes) was assessed during the diagnosis of problematical lymphoid tissue biopsy specimens. In 14 of 18 specimens (78%), which contained a malignant lymphoproliferation of uncertain aetiology, this technique permitted the demonstration of a monoclonal proliferation of B cells (nine cases) or T cells (five cases). In five further lymph node biopsy specimens, in which the differential diagnosis lay between a reactive or malignant process, a clonal proliferation was shown in three cases. DNA analysis is, therefore, of practical value in resolving many of the diagnostic problems that arise in the assessment of lymphoid tissue biopsy specimens.

B-Lymphocytes↗

Survival in breast cancer related to tumour oestrogen receptor status and immunohistochemical staining for NCRC 11.

NCRC 11 is a monoclonal antibody raised against dissociated breast cancer cells. Using this antibody, it has been shown in an earlier study that staining of a high proportion of tumour cells is strongly associated with superior survival. Many investigators have found that positive tumour oestrogen receptor (OER) status is associated with better survival in breast cancer. In the present study of 136 breast cancer patients followed up for a minimum of 30 months, tumour oestrogen receptor assays were carried out, and using the indirect immunoperoxidase technique, histological sections of paraffin embedded material were stained for NCRC 11; for the purpose of this study, tumours showing 25 per cent or less cells staining were regarded as 'negative'. Patients whose tumours were OER positive had a significantly better prognosis (logrank test P less than 0.05). Patients whose tumours were graded as negative for NCRC 11 had a poorer prognosis compared with the positive group but this did not attain significance. Our failure to demonstrate convincingly a better prognosis for the NCRC 11 positive patients may relate to the shorter duration of our study, or to different tissue fixation techniques. In this study staining for NCRC 11 was positively correlated with oestrogen receptor status (P less than 0.02).

Antibodies, Monoclonal↗

Nasal neuroblastoma secreting vasopressin. A case report.

A patient with a nasal neuroblastoma was found to have hypertension and severe hyponatraemia. Radiotherapy and cytotoxic chemotherapy were ineffective in reducing the size and vascularity of the neoplasm. Assay of tumor tissue post mortem revealed high levels of arginine vasopressin. The possibility of vasopressin formation to be added to the better known potential hormonal secretory activities of neuroblastomas.

Adolescent↗

Lomustine, vindesine and bleomycin (LVB) used in the treatment of relapsed advanced Hodgkin's disease. A prospective study on behalf of the East of Scotland and Newcastle Lymphoma Group (ESNLG).

Sixty-three patients with relapsed advanced Hodgkin's disease were treated with lomustine (CCNU), vindesine and bleomycin (LVB). Age range was 17-72 years, with 38 males and 25 females. Thirty patients achieved complete remission (CR) with a median duration of 24+ months (range 3-55). Nineteen continue in unmaintained CR. CR rates were highest for those patients who relapsed greater than 6 months after first line treatment and for those at second or subsequent relapse. CR rates were higher in those with nodal only relapse. Twenty-seven patients were non-responders and six were partial responders. These 33 patients were subsequently changed to alternative chemotherapeutic regimes and 26 failed to respond to any therapy and have since died. Only one patient is in unmaintained complete remission. The regimen was well tolerated by patients, and easy to administer. It produced no serious episodes of toxicity. We conclude that LVB is of value in the management of relapsed advanced Hodgkin's disease especially in chronic relapsing patients, and where relapse occurs greater than 6 months after the first line treatment. We are presently unsure whether it offers any advantage over reintroduction of first line treatment in the latter group.

Adolescent↗

A simple method for assessing quinine pre-treatment in acute malaria.

Administration of a loading dose of quinine in severe malaria may be dangerous if therapeutic blood concentrations are already present because of previous treatment. To assess the reliability of the history of pretreatment we conducted a prospective study of 379 adult patients with acute falciparum malaria admitted to a hospital in western Thailand. Admission plasma concentrations of quinine were measured by high performance liquid chromatography (HPLC), and compared with the patients' history of previous quinine treatment. The sensitivity of the history was 59% (95%) confidence interval [CI] 49-69%), the specificity was 79% (95% CI 74-84%), the positive predictive value was 53%, and the negative predictive value 82%. A rapid (10 min semi-quantitative estimate of plasma quinine concentrations, based on simple 'dipstick' method using a quinine-specific monoclonal antibody, proved considerably more sensitive and specific. The correlation between the dipstick estimate and the subsequent HPLC measurement of plasma quinine concentration was 0.85 (n = 404; P < 0.0001). In 404 admission samples, the negative predictive value of the dipstick estimate for plasma quinine concentrations > 1 microgram/mL was 100%. In Thailand the history of previous quinine treatment given by the patients or their relatives was unreliable but the quinine dipstick provided a simple and rapid means of assessment of quinine pre-treatment in acute falciparum malaria.

Acute Disease↗

Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria.

Nitric oxide is an important host defence molecule as well as being a mediator in many pathophysiological processes. To investigate its role in severe malaria, we measured plasma nitrate and nitrite concentrations in 70 children with malaria (54 with severe malaria) and 48 control subjects (33 with medical conditions and 15 surgical patients). We related these measurements to plasma lactate concentrations, an established marker of disease severity in malaria. Plasma lactate levels were significantly elevated in patients with deep coma (P = 0.0007) and those with a fatal outcome, but mean nitrogen oxide concentrations were not significantly different in the 2 outcome categories and were not related to depth of coma (P > 0.5). In patients whose cerebrospinal fluid (CSF) was examined, lactate concentrations were elevated in fatal cases (geometric mean 8.2 mmol/L, n = 5) compared with survivors (3.4 mmol/L, n = 13; P = 0.032); corresponding CSF nitrogen oxide concentrations were 10.7 microM in fatal cases compared with 12.5 microM in survivors (P = 0.5). Plasma nitrogen oxide concentrations were negatively correlated with admission parasitaemia (r = -0.41, n = 70; P < 0.0001). In our population, elevations of plasma lactate, but not nitrite or nitrate, reflected disease severity in malaria.

Biomarkers↗

Semi-quantitative measurement of Plasmodium falciparum antigen PfHRP2 in blood and plasma.

Plasmodium falciparum histidine rich protein 2 (PfHRP2) antigen was measured semi-quantitatively in whole blood, plasma, and supernatants and red blood cells of cultures in vitro using the dipstick ParaSight-F test and also by a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA). In vitro, PfHRP2 was secreted mainly during the second half of the asexual cycle with a marked rise during schizont development and rupture. The total PfHRP2 secreted before schizogony corresponded to approximately 4% of that contained in the red blood cells. In samples from 55 patients with acute falciparum malaria, the level of detection by ELISA corresponded to parasitaemias of 100/microL for whole blood and 1600/microL for separated plasma. Whole blood PfHRP2 levels were correlated significantly with admission parasitaemia (r = 0.76, P < 0.0001) and the stage of parasite development (r = 0.43, P < 0.01). Although whole blood PfHRP2 concentrations were higher in severe malaria, plasma concentrations of PfHRP2 were considerably higher in severe malaria (median titre 1:320, range zero to 1:1280) than in uncomplicated malaria (median titre 1:5, range zero to 1:80; P < 0.0001). The ratio of whole blood to plasma PfHRP2 was lower in severe than in uncomplicated malaria (median 4, range 0.25 to 256, versus 64, range 4 to 1280; P < 0.0001). With plasma samples the intensity of colour change on the dipstick correlated well with more precise measurement of optical density in the ELISA (r = 0.88, P < 0.0001). These results suggest that measurement of PfHRP2 in plasma could provide an alternative approach to the assessment of the parasite biomass, and thus prognosis, in severe malaria, and that this could be done simply by using the currently available dipsticks.

Adolescent↗

p53 immunostaining as a marker of malignancy in cytologic preparations of body fluids.

The accurate identification of suspicious cells in cytologic preparations is a common problem in diagnostic cytopathology. Recent studies have shown that mutation of the p53 gene may be the most common genetic event in human malignancy. Mutation leads to altered conformation and increased half-life of the p53 protein, resulting in detectability by immunocytochemistry. The usefulness of p53 immunocytochemical staining as a marker of malignancy in the cytologic analysis of body fluids was investigated in the present study. One hundred fifty-four serial samples of body fluids submitted for cytologic diagnosis were also examined for p53 immunoreactivity. Of 121 cases reported as cytologically benign, 3 (2.5%) stained positively for p53; 16 samples were cytologically malignant, and 7 (43.7%) of these were positive for p53 (P < .001). Of those reported as suspicious but not conclusively malignant, 4 of 17 (23.5%) showed p53 immunoreactivity. On review, two of the three patients whose samples were benign cytologically yet showed positive p53 staining had histologic evidence of malignancy. The third patient died without a postmortem examination. Of the 17 cytologically suspicious cases, 16 (94.1%) were later proven to be malignant, and p53 was positive in 4 (25%). These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of body fluids. The presence of p53 immunoreactivity in cytologic samples is strongly suggestive of malignancy, though its absence does not exclude neoplasia.

Body Fluids↗

Prediction of nodal metastasis and prognosis in breast cancer: a neural model.

BACKGROUND: An increasing number of women with breast cancer are detected with the disease at an early stage, when the lymph nodes are not involved. In order to obviate the necessity to carry out axillary dissection, accurate surrogates for lymph node involvement need to be identified. In this paper we have examined the use of a neural network to predict nodal involvement. The neural approach has also been extended to investigate its predictive applicability to the long-term prognosis of patients with breast cancer. A number of established and experimental prognostic markers have been studied in an attempt to accurately predict patient outcome 72 months after first examination. METHODS: 81, unselected patients, presenting clinically, who had all undergone mastectomy for invasive breast carcinoma were considered in this study. A total of 12 markers were analysed for the prediction of lymph node metastasis, while node status itself was used as an additional marker for the prognostic analysis. In this case the outcome related to whether a patient had relapsed within 72 months of diagnosis. In both cases, a number of marker combinations were analysed separately in an attempt to classify those most favourable marker interactions with respect to lymph node prediction and prognosis. Patients were randomly divided into a training set (n = 50) and a test set (n = 31). The simulation was developed using the NeuralWorks Professional II/Plus software (NeuralWare, Pittsburgh, Pa, USA). RESULTS: In the case of lymph node metastasis, the neural network was able to correctly predict axillary involvement, or otherwise, in 84% of the patients in the test set by considering 9 of the 12 available markers. This represents an improvement of 10% over the traditional approach which considers the tumour grade and size only. The sensitivity and specificity were also shown to be 73% and 90%, respectively. With regard to patient prognosis, again 84% classification accuracy was obtained using a subset of the markers, with a sensitivity of 50% and a specificity of 96%. CONCLUSIONS: Although this study considered a relatively small sample of patients, nevertheless it demonstrates that artificial neural networks are capable of providing strong indicators for predicting lymph node involvement. There is no longer a need for axillary dissection with all its implications in patient morbidity and demands on clinical resources. The management of breast cancer and the planning of strategies for adjuvant treatments is also facilitated by the use of neural networks for the long-term prognosis of patients.

Biomarkers, Tumor↗