Biomedical subjects

M J Higgs

Publications and source records attributed to M J Higgs.

14 recordsLinked to original sources

PubMed2001

MUC1 expression in primary breast cancer: the effect of tamoxifen treatment.

This was a non-randomised single institution retrospective study. Forty-six banked frozen tumour specimens were obtained from a group of patients who had undergone 3 weeks of neoadjuvant treatment with tamoxifen between biopsy and surgery. Fifty-one comparison specimens were randomly selected from a group of concomitantly treated primary breast cancer patients who did not receive neoadjuvant tamoxifen. Specimen selection was not based on prognostic factors: hormone receptor status, patient age, or menopausal status. MUC1 expression and cell cycle distribution were assessed by flow cytometry. S-phase fraction of MUC1 positive and MUC1 negative cells were compared. A lower percentage of cells expressed MUC1 following 3-week tamoxifen treatment 18.2% versus 28.5% (p = 0.03, Mann-Whitney) and lower levels of MUC1 expression were seen following tamoxifen treatment 31,519 molecules/cell versus 39,387 (p = 0.04, Mann-Whitney). MUC1 positive cells, irrespective of treatment group, had a greater proportion of cells in S-phase of the cell cycle 27.9% versus 16.8% (p = 0.0004, Mann-Whitney) and demonstrated more cases of aneuploidy 80.65% versus 42.6% (p < 0.0001). MUC1 levels in primary tumours treated neoadjunctively with 3 weeks of tamoxifen were lower than a comparison group which did not receive tamoxifen. MUC1 should be explored further as an intermediate biomarker for assessment of treatment and prognosis.

Aged↗

PubMed1998

Cytokeratin expression in breast cancer: phenotypic changes associated with disease progression.

Transition from a normal to a cancerous state is marked by alterations in the cytoskeletal structure of those cells involved. We have examined such changes to determine if these transitions are markers of disease progression. Cytokeratin (CK) protein and messenger RNA (mRNA) expression were examined in malignant and benign breast tissues. Flow cytometric results demonstrated a significant correlation between cytokeratin protein expression detected by 5D3 antibody, specific for cytokeratins 8, 18, and 19 and axillary node metastasis (P = 0.01). A threshold of positivity of 338,000 molecules/cell was determined and reflected the wide range in cytokeratin levels expressed by normal or benign tissues. Examination of cytokeratins 8, 18, and 19 revealed a consistent pattern of expression with respect to tumor grade. Only cytokeratin 19 showed significant correlation with increasing tumor size (P = 0.006). mRNA expression for cytokeratin 8 was significantly higher in node-positive compared with node-negative disease (P = 0.02). Cytokeratin 18 mRNA levels were significantly lower in both node-negative (P = 0.03) and node-positive (P = 0.02) patients when compared with benign samples. Increased levels of cytokeratin 18 mRNA showed an inverse relationship with protein expression (P = 0.05). The results indicate that cytokeratin expression in breast cancer may be associated with tumor progression. Furthermore, the alteration in the expression of individual cytokeratins deserves further investigation to determine the consequences of these changes with respect to cellular function.

Adult↗

PubMed1998

The effect of 3-week tamoxifen treatment on oestrogen receptor levels in primary breast tumours: a flow cytometric study.

The effect of 3-week, preoperative tamoxifen treatment on oestrogen receptor (ER) levels, expressed by primary breast tumours, was examined. Patients (age-matched) with breast cancer, confirmed by fine-needle aspiration, were either treated with 20 mg ml(-1) oral tamoxifen per day or received no medication in the 3-week interval between assessment and surgery. Quantification of ER using flow cytometry was performed on the surgically removed tumour samples from tamoxifen-treated (n = 40) and control (n = 38, untreated) patient groups. The tumours were mechanically disaggregated, and saponin treatment rendered these cells permeable to antibodies. Using dual-parameter labelling with a FITC-conjugated antibody (NCL-5D3) directed against cytokeratin 8/18/19 and a biotinylated antibody (DAKO-ER 1D5) directed against the oestrogen receptor, ER quantification was determined on a number of receptors per cell basis. Using QC quantum bead standards, ER levels in the epithelial cell population, the non-epithelial cell population and the whole-cell population (ER+) were calculated. ER levels were significantly lower in the total cell population than tamoxifen-treated patients (P = 0.002) when compared with the control (untreated) group. By using a gating procedure using 5D3 antibody positivity, a significantly lower level was detected on examining the cytokeratin-positive population alone (P = 0.006). Using a complementary gating technique, ER levels were quantified in the cytokeratin-negative cell population. Examination of this group of cells showed no significant difference between the levels of oestrogen receptor found in the tamoxifen-treated and untreated groups (P = 0.4). We have demonstrated that ER levels can be monitored by flow cytometry. ER levels in patients treated with tamoxifen 3 weeks before operation are significantly lower than in a comparative group of patients who received no drug. Furthermore, the most significant difference in receptor levels is seen by quantification of total ER levels expressed by all the tissue.

Antineoplastic Agents, Hormonal↗

PubMed1997

The pathological and biological nature of screen-detected breast carcinomas: a morphological and immunohistochemical study.

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from 'clinical' cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history.

Biomarkers, Tumor↗

PubMed1996

Examination of multidrug resistance in cell lines and primary breast tumours by flow cytometry.

The aim of this study was to measure multidrug resistance (MDR) by flow cytometry and quantify the expression of P-glycoprotein (using antibody) glutathione transferase (using alpha-GSTpi antibody) in alpha-JSB-1 and alpha-GSTpi of a series of cell lines and primary breast cancers, and to assess the relationship between these MDR proteins and a selection of oncogene and prognostic markers in breast cancer. Flow cytometry was performed using permeabilised cells stained with fluorescent antibodies using well-established methods. Antibody staining was confirmed for JSB1, but not GSTpi by use of known positive and negative controls. No correlation was seen when comparing the number of molecules of alpha-JSB-1 with alpha-GSTpi (P = 0.1, r2 = 0.4, n = 14) using a selection of cell lines. Examination of 45 breast tumours for expression of JSB-1 and GSTpi revealed a significant association between these two antibodies (P < 0.00001, r2 = 0.5, n = 45). On examining the breast tumours, alpha-JSB-1 showed a positive association with c-erbB-2 (P = 0.003), c-myc (P = 0.0004) and c-jun (P = 0.02) but not ER or EGF-R expression. alpha-GSTpi showed a positive association with c-erbB-2 (P = 0.03) and c-myc (P = 0.0004) but not ER, EGF-R or c-jun. Flow cytometric MDR levels were not related to tumour grade or axillary node status. In solid tumours, a relationship between the two antibodies used has been clearly demonstrated, however, specificity of alpha-GSTpi is questioned. Both antibodies show an association with c-erbB-2, which is associated with poor prognosis and with c-myc which is involved in cell cycling and differentiation. Monitoring MDR markers (Pgp) using this methodology may be useful for evaluation of prognosis in breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

The relationship between flow-cytometric and immunohistochemically detected c-erbB-2 expression, grade and DNA ploidy in breast cancer.

Quantification of c-erbB-2 and its relationship with other prognostic markers using flow cytometry has been examined. In this study a level for c-erbB-2 expression above which tumours are classified as positive by flow cytometry has been determined by employment of positive cut-off threshold levels. c-erbB-2 expression by both flow cytometry and immunohistochemistry was studied using the monoclonal antibody NCL-CBII. The relationship of c-erbB-2 quantification by flow cytometry was then compared with ploidy, axillary node status, tumour size and grade. Increased c-erbB-2 expression was seen using flow cytometry. Correlation between immunohistochemistry and flow-cytometry methods just failed to reach significance (P = 0.06). Immunohistochemistry revealed a significant relationship between c-erbB-2 expression and aneuploidy (P = 0.04). Cytokeratin-positive cells from 110 samples obtained from patients with breast cancer were assayed for DNA content and c-erbB-2 expression by flow cytometry. No correlation was seen between these parameters upon application of Mann Whitney analysis. However, examination of fluorescence thresholds showed a positive correlation between grade and c-erbB-2 expression at a level of more than 3200 molecules (P < or = 0.03). At the level of 3600 molecules significance was increased (P = 0.004). These levels equated with between 15% and 19% of the samples being classified as c-erbB-2-positive. Application of these cut-off points showed no correlation between c-erbB-2 expression and ploidy, tumour size or axillary node status. Comparison of ploidy and grade showed a significant association (P = 0.0015), increased grade correlating with aneuploidy.

Adult↗

PubMed1995

p53 expression measured by flow cytometry. A comparison of three monoclonal antibodies and the relationship with grade and DNA ploidy in breast cancer.

The aim of this study was to quantify p53 expression by flow cytometry. A panel of three monoclonal antibodies: NCL-p53-240, NCL-p53-1801 and NCL-p53-DO7, was tested on breast cell lines and primary breast cancers. The relationships between ploidy, tumour grade and p53 expression for each antibody, were examined. Methodology was assessed using a variety of breast cell lines. Staining patterns were confirmed and the quantification technique qualified. Cytokeratin-positive cells from 58 samples obtained from patients with breast cancer were assayed for DNA content and p53 expression. p53 quantification was performed using calibrated fluorescent beads on cytokeratin-positive cells. Bloom and Richardson grading revealed 20 grade I and 38 grade II/III breast cancers. Examination of fluorescence thresholds showed a positive correlation between grade and DO7 (P = 0.003) at a level of 8900 molecules, 240 (P = 0.005) at a level of 2900 molecules and 1801 (P = 0.005) at a level of 1850 molecules. These levels equated with 34% (DO7), 43% (240) and 43% (1801) of the samples being classified as p53-positive. Examination of ploidy revealed 23 diploid and 35 aneuploid breast cancers. Application of p53 threshold levels on diploid and aneuploid tumours showed correlation between aneuploidy and p53 expression for DO7 at a level of 9000 molecules, 240 at a level of 1900 molecules and 1801 at a level of 1800 molecules. These levels equated with 34% (DO7), 52% (240) and 52% (1801) of the samples being classified as p53-positive. We conclude that measurement of p53 by flow cytometry may be of clinical importance by indicating levels of positivity using fluorescence thresholds. p53 expression has been shown to correlate with both grade and ploidy. Flow-cytometric measurement of p53 may be a useful prognostic assay.

Aneuploidy↗

PubMed1995

Correlation of the endoscopic appearance with clinical outcome for submucous Polytef paste injection in vesico-ureteric reflux.

The endoscopic injection of Polytef paste is now a well established method of treating vesico-ureteric reflux. In this study the video tapes of 64 treatments were independently reviewed to assess any predictors of failure. The visual appearance of the mound of paste was found to correlate with the clinical outcome, except when less than 0.2 mL of paste was used for smaller ureteric orifices, or when the ureteric orifice was large enough to admit the 9.3 FG cystoscope. In cases with a large ureteric orifice effective treatment was achieved without the neat crescent-on-a-mound appearance, provided a larger than average volume of paste was used. Meticulous placement of the needle was also shown to be important if success was to be ensured.

Endoscopy↗

PubMed1993

Screening for breast cancer detects tumours at an earlier biological stage.

Between August 1988 and July 1990, 17,678 women in the Gateshead, Sunderland, South Tyneside and Durham districts attended the national breast screening programme. A total of 131 cancers were detected. The morphology of cancers detected by screening was compared with that of tumours in 71 patients presenting clinically in the same period. Screen-detected cancers included a higher proportion of tumours of more favourable histological grade and type, were smaller in size and had less axillary lymph node involvement than those detected clinically. Survival was predicted from the Nottingham Prognostic Index. Patients with screen-detected cancer had an expected survival advantage (95 per cent confidence interval) of 26.5 (12.3-40.6) per cent at 5 years, 26.5 (11.8-41.2) per cent at 10 years and 29.1 (14.5-43.7) per cent at 15 years. This survival advantage in screened patients expected at 5, 10 and 15 years is consistent with the 30 per cent reduction in mortality rate demonstrated in the Health Insurance Plan study and the Swedish two counties trial.

Breast Neoplasms↗

PubMed1991

Breast abscess following central venous catheterization.

We describe a case of late perforation of the right internal mammary vein by a central venous catheter inserted via the left subclavian vein. This resulted in extravasation of parenteral nutritional fluid and breast abscess formation. Delay in reaching the diagnosis was experienced in this case and in two cases previously reported. The clinical presentation was similar in all three cases with good early function of the catheters followed by symptoms of chest pain and signs of inflammation in the breast contralateral to the site of insertion of the central venous catheter. Confirmation of correct placement of the central venous catheter must be sought in any patient who develops these symptoms or signs so that the delay in diagnosis we experienced can be avoided. This may be obtained by a lateral or oblique chest radiograph or by contrast studies if preferable.

Abscess↗

PubMed1990

Urinary infection following out-patient flexible cystoscopy.

Of 161 flexible cystoscopies performed in an out-patient endoscopy suite, the incidence of urinary tract infection was 7.5%. Infection rates were higher in patients with a history of previous urinary tract infection or where an additional procedure was also performed. No difference was noted between the infection rates in men and women.

Ambulatory Care↗

PubMed1985

Mucosal abnormalities at the anastomosis site in patients who have had intestinal resection for colonic cancer.

Twenty eight patients with colonic cancer, who were asymptomatic after intestinal resection and anastomosis, underwent colonoscopy as part of their routine follow up, and biopsies were obtained from the anastomosis and several other sites. Sections were stained by haematoxylin and eosin, several methods for mucin, and by the peroxidase-antiperoxidase method for carcinoembryonic antigen. Non-specific inflammatory changes were seen at the anastomosis in 11 of the 28 cases, apparent in several two years after operation; focal surface ulceration was seen in over half these samples. Neither dysplastic nor adenomatous change was detected, but at seven anastomoses the so called transitional change, which has been regarded as a preneoplastic change, was apparent. There was no consistent alteration in carcinoembryonic antigen reactivity. It is concluded that there is morphological evidence of a continued stimulus to regenerative activity at some anastomoses and that this may represent a promoting factor enhancing further carcinogenesis.

Adenocarcinoma↗

PubMed1975

Appendicitis and mimicking conditions. A prospective study.

A prospective study of 444 consecutive patients diagnosed as having acute appendicitis was carried out in a district general hospital. The appendix was acutely inflamed, gangrenous, or perforated in 346 patients. Diagnostic error, 22% overall, was twice as common in females as in males. Organisms were isolated from the outer appendix wall in 117 patients, isolation increasing with the severity of inflammation. 12% of children under 11 had mesentric adenitis, 10% of all females had gynaecological lesions, and 14% of patients over 50 had acute diverticulitis. In only 6% of patients was no abnormality found at operation, and in every case the disorder was dealt with through the gridiron incision.

Abdomen, Acute↗

PubMedDate not supplied

Acute appendicitis presenting with surgical emphysema and pneumomediastinum.

A case is reported of a young man presenting with abdominal pain and surgical emphysema of the neck. A chest x-ray revealed pneumomediastinum but other investigations excluded oesophageal rupture. He was found to have a complicated acute appendicitis. The history and likely causes of this unusual presentation of a common complaint are reviewed.

Adolescent↗