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M Leader

Publications and source records attributed to M Leader.

At least 55 records · Page 3Linked to original sources
PubMed1994

C-erbB-2 immunostaining: problems with interpretation.

AIMS: To assess the consistency and reproducibility of assessment of c-erbB-2 immunostaining, and to examine some of the problems relating to inter- and intraobserver variability in the documentation of positive staining; to profile the spectrum of cytoplasmic and membranous staining in a wide range of tumour types. METHODS: A total of 283 neoplasms were examined for immunohistochemical expression of the c-erbB-2 oncoprotein. Three independent observers were required to assess intensity both of membrane and cytoplasmic staining on a three point and then a four point scale. Extent of positive staining was also assessed on a two point scale. A minimum of two weeks elapsed between assessments using the differing scales. RESULTS: Positive membrane staining was documented by one or more observers in 16.6% of tumours examined. This positivity was largely restricted to bladder, renal, and breast tumours. The overall level of disagreement as to the presence or absence of membranous staining was 11.3%. Cytoplasmic staining was identified in 55.5% of tumours studied. The level of disagreement as to the presence or absence of cytoplasmic staining was 26.5%. CONCLUSIONS: Intraobserver variability was minimal, indicating that each pathologist was adhering to internal reproducible standards. Interobserver variability was greater, indicating that the interpretation of c-erbB-2 immunostaining may require set guidelines. It is suggested that assessment should be referenced to a standard positive control, that a three tier system for grading of intensity and a two tier system for grading of extent should be adopted, and that the evaluation should be agreed by at least two pathologists. The presence of cytoplasmic staining should continue to be routinely recorded until its biological role and clinical implications are fully understood.

Biomarkers, Tumor↗
PubMed1993

Deoxyribonucleic acid ploidy studies in choroidal melanomas.

In several tumors of different organ sites, the amount of DNA in a cell (ploidy) is associated with malignancy. We performed DNA quantitation in 21 choroidal melanomas and compared flow cytometry with image analysis in 11 of these melanomas. We modified our preparation technique to overcome problems with pigment and control cell populations in the image analysis group. Fifteen tumors were diploid and two tumors were tetraploid. Four tumors were unprocessable by flow cytometry, but two of these tumors were diploid by image analysis. Image analysis also detected tetraploidy in two tumors that were diploid by flow cytometry. During image analysis, cells were classified according to the Callendar classification and histograms were plotted for each cell type. All spindle A cells were diploid and most tetraploid peaks were formed by epithelioid cells. The use of image analysis on small samples of choroidal melanomas may be of value both in confirmation of diagnosis and prognosis of these lesions, and perhaps therapeutically, for example, in the monitoring of radiation treatment.

Choroid Neoplasms↗
PubMed1993

Oxygen free radicals and acute pancreatitis: fact or fiction?

The effect of oxygen free radical suppression was studied in the taurocholate model of acute pancreatitis in the rat using systemic allopurinol, superoxide dismutase (S.O.D.) and catalase. None of the treatments were beneficial which suggests that oxygen free radical suppression is unlikely to be clinically beneficial in acute pancreatitis.

Acute Disease↗
PubMed1993

c-myc expression in renal carcinoma: correlation with clinical parameters.

There is evidence that c-myc is expressed in renal carcinomas and that it is associated with histological grade. This study reports on the clinical correlations of oncogene expression and clinical features of the disease. Tissue sections from 97 patients (95 primary and 12 secondary cancers) were immunostained with a c-myc oncoprotein antibody. The tumours were scored for extent and intensity of nuclear and cytoplasmic staining. Ninety patients were suitable for follow-up study. High levels of expression correlated significantly with increasing T category and nuclear grade, as well as with venous invasion. No correlation with nodal involvement, the presence of metastases, tumour architecture or cell type was found. The extent of nuclear staining was related to survival (although not to recurrence), but in a multivariate analysis did not provide independent prognostic information. It was concluded that semiquantitative assessment of levels of c-myc oncoprotein does not provide clinically useful prognostic information.

Adult↗
PubMed1993

Ploidy and prognosis in renal carcinoma.

The value of tumour ploidy status as a prognostic indicator in renal carcinoma is disputed. In this retrospective study the DNA content of 90 primary and 10 secondary renal cell carcinomas was measured using flow cytometry. Data on recurrence and survival were available in all cases. Tumours were staged according to the TNM system and histological grade was based on nuclear morphology. Formalin-fixed, paraffin-embedded material was processed using standard techniques. Multiple samples were examined in 19 cases. Of the primary tumours, 52 were diploid, 24 were aneuploid and 6 were tetraploid; 8 patients had uninterpretable histograms. Ploidy of the secondary tumours was similar to that of their respective primaries. Aneuploidy correlated with higher grade but not with TNM category and, although associated with an increased risk of death, did not provide independent prognostic information. Heterogeneity of ploidy was found in 6 of the 19 cases where more than 1 sample was assessed. It was concluded that tumour DNA content in renal carcinoma is weakly linked to outcome, is subject to sample error and does not provide accurate prognostic information as a single independent variable.

Adult↗
PubMed1993

Comparison of flow and static image cytometry in the determination of ploidy.

AIMS: To compare the efficiency of flow cytometry and computed image cytometry; and to see if a reliable set of guidelines regarding interpretation of histograms could be drawn up. METHODS: The two methods were applied to a series of 111 formalin fixed renal cell carcinomas. Data generated by both methods were compared. RESULTS: The methods agreed in 85 cases. Hypodiploidy was detected by computed image cytometry in seven cases in which flow cytometry had shown only an aneuploid peak. Aneuploidy in seven in which the corresponding flow cytometry histogram was diploid. There was an overlap in the second peak proportions on flow cytometry histograms between those classed as diploid or tetraploid by computed image cytometry. In six cases the flow cytometry histograms had unacceptably high coefficients of variation and in all of these cases computed image cytometry demonstrated aneuploidy. CONCLUSIONS: Computed image cytometry is particularly useful for clarifying difficult areas in flow histograms--specifically, high coefficients of variation, high G2M phase, as well as possible near diploid aneuploidy and hypodiploidy.

Carcinoma, Renal Cell↗
PubMed1993

Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis.

This retrospective study reports the incidence of hydatidiform mole in a population of 19,457 pregnancies over a 3-year period. During the study period all "products of conception" from first and second trimester abortions were referred for pathological examination. Coded histologic sections were reviewed using the published histologic criteria for hydatidiform mole. Ploidy was estimated by DNA flow cytometry. Clinical data were retrieved from maternal case notes. Thirty-eight cases were confirmed as hydatidiform mole, 10 (26%) as complete mole, and 28 (74%) as partial mole. Twenty-three cases of partial mole (88%) were triploid, and nine of 10 complete moles were diploid. The incidence of hydatidiform mole was 1:512 pregnancies, (complete mole, 1:1,945; partial mole, 1:695). Only one case (3.5%) of partial mole was suspected clinically. One case of persistent gestational trophoblastic disease occurred following a complete mole. No sequelae were encountered following partial mole. We conclude that hydatidiform mole is a common condition and the majority of cases are partial moles. Quantitatively imprecise morphologic criteria contribute to the inaccuracy in reporting of partial mole; analysis of ploidy is useful in the evaluation of problem cases. Follow-up of partial mole is warranted because its true biological potential is as yet unclear.

Abortion, Spontaneous↗
PubMed1992

DNA quantification of squamous cell carcinoma of the oesophagus by flow cytometry and cytophotometric image analysis using formalin fixed paraffin embedded tissue.

This is the first comparative study of DNA quantification of oesophageal squamous cell carcinoma by flow cytometry (FCM) and image cytometry (ICM) using formalin fixed paraffin embedded tissue. The potential advantages of ICM include the identification of a reliable control cell population; avoidance of non-tumour stromal and inflammatory cell nuclei, nuclear fragments, degenerate cell nuclei and doublets, triplets etc., which are not possible with FCM using archival tissue. Twenty-eight cases, all of the same stage (stage 2a) and similar grade (well or moderately differentiated) were analysed. The cases were separated into two groups, those that had succumbed to tumour in less than 18 months (group A) and those that were tumour free at least 18 months post-resection (group B). Using ICM all 28 tumours yielded interpretable histograms by comparison to 25 of 28 using FCM. Aneuploidy was identified in 100% of cases in group A using ICM (in comparison to 73% by FCM) and in 73% of group B using ICM (in comparison to 44% by FCM). Any tumour aneuploid by FCM was also aneuploid by ICM. Nine cases aneuploid by ICM were euploid by FCM. The mean 5C exceeding rate (% of cells whose nuclei contain a DNA mass equivalent to > 5 sets of 23 chromosomes) was 21% in group A and 14% in group B (P < 0.01). Euploidy was confined to tumours of those patients disease free for more than 18 months. The conclusions of this study are that: firstly, ICM is superior in its yield of interpretable histograms to FCM using formalin fixed paraffin embedded tissue; secondly, ICM is more sensitive in the identification of aneuploid stemlines than FCM; and thirdly, euploid tumours (as detected by ICM) appear to have a better prognosis than aneuploid tumours of similar stage and grade.

Adult↗
PubMed1992

Emergency appendicectomy: a one year audit.

A retrospective study of emergency appendicectomy over a one-year period at Beaumont Hospital was carried out. The overall normal appendicectomy rate was 22.8%, and was twice as high in women (31%) as in men (15%). Gangrenous or perforated appendicitis was present in 20% of cases. The overall mean assessment-surgery interval was 16.7 hours. Considerable variation in the use of antimicrobial agents was noted in the study, and many haematological and radiological investigations performed did not appear to improve diagnostic accuracy. Among patients with clinical features typical of appendicitis, 16% proved to have a normal appendix. These results point to a number of aspects of the diagnosis and management of appendicitis where there appears to be room for future improvement.

Acute Disease↗
PubMed1992

DNA ploidy in squamous oesophageal carcinoma.

The role of DNA ploidy in the management of oesophageal carcinoma is unclear. Most studies have employed flow cytometry (FC) for DNA analysis but some have used image analysis (IA) of tissue sections. In this study aneuploidy rates in stage IIa squamous tumours were determined by both FC and IA of cell suspensions and results were compared with outcome in two patient subgroups. Group 1 (n = 15) were patients who died from tumour recurrence within 1 year of surgery while Group 2 (n = 21) were patients who survived tumour free for at least 1 year. Aneuploidy rates differed significantly between techniques; 29 of 36 tumours (81%) were aneuploid by IA compared with 19 of 34 (56%) by FC (P < 0.05). Aneuploidy rates differed significantly between groups 1 and 2 as determined by FC (79%) versus 40%) (P < 0.05) but not by IA (93% versus 71%) (P = ns). Euploid status was a good prognostic indicator; 6 of 7 (86%) patients with euploid tumours by IA and 12 of 15 (80%) by FC (P < 0.05) survived more than 1 year. The sensitivity and specificity of euploidy was 93% and 28.6% for IA compared with 78.6% and 60% for FC. Since 33 (92%) of these tumours exhibited a marked peritumoral desmoplastic or chronic inflammatory reaction IA, being more sensitive to subtle nuclear change, may be a more appropriate technique than FC for evaluation of the role of ploidy in such tumours.

Adult↗
PubMed1992

Specificity of colon specific antigen and colon ovarian tumour antigen.

Sections (5 microns thick) from 101 primary adenocarcinomas (including ovarian, colorectal, gastric, breast, oesophageal, prostatic, pancreatic, endometrial and gall bladder) were incubated wtih anticolon specific antigen (CSA) and anticolon ovarian tumour antigen (COTA) antibodies using the peroxidase antiperoxidase technique with positive and negative controls. Anti-CSA positivity was seen in 19 of 20 colonic adenocarcinomas, but it was also seen in a large number of the other tumours. While anti-COTA staining was positive in 16 of 20 colonic adenocarcinomas and 20 of 30 ovarian adenocarcinomas, it was also positive in a large number of the tumours. Anti-CSA and anti-COTA are not adequately specific in the identification of a colonic or ovarian origin of an adenocarcinoma and cannot reliably be applied to the identification of a metastatic adenocarcinoma of unknown primary site.

Adenocarcinoma↗
PubMed1992

DNA quantitation of Wilms' tumour (nephroblastoma) using flow cytometry and image analysis.

AIMS: To compare flow cytometry (FCM) with image analysis (IA) in the DNA quantitation of Wilms' tumour (WT) and to correlate data so obtained with recognised clinical and pathological prognostic parameters. METHODS: Thirty six patients with histologically proved WT diagnosed between 1980-89 were investigated. Fifteen patients had stage I disease, 10 stage II, six stage III, two stage IV and three stage V. Suspension of nuclei obtained by pepsin digestion of paraffin wax embedded tumour tissue was analysed using a FAC-Scan flow cytometer, and a CAS-100 image analyser. RESULTS: Tumours were concordant in most instances, however, IA identified aneuploidy in two tumour samples which were diploid by FCM. Aneuploidy was detected in 5/33 tumours with favourable histology and 3/3 with unfavourable histology. Three of 28 patients with Stage I, II and V disease and 5/8 patients with stage III and IV had aneuploid tumours. All patients with unfavourable histology died of disease. In the group with favourable histology, 4/5 patients with aneuploid tumours developed recurrent disease compared with 1/27 diploid tumours (p less than 0.0001). CONCLUSIONS: Ploidy may be a useful additional prognostic indicator in Wilms' tumour with favourable histology. Larger scale studies are needed to confirm the relation of ploidy to survival in early stage WT.

Child↗
PubMed1992

Image analysis in the determination of ploidy and prognosis in renal cell carcinoma.

The usefulness of ploidy determination by flow cytometry in renal cell carcinoma is disputed. An alternative technique for DNA quantitation, computerised static image analysis, has several advantages over flow methods. Tissue from 90 cases of primary renal cell carcinoma was analysed by image analysis. Cases were assigned a histological grade and staged and stratified by the TNM system. Fifty-two cases were diploid, 28 were aneuploid and 9 were tetraploid (1 was unanalyzable). Heterogeneity of ploidy was noted in 4 cases. The degree to which nuclear DNA content exceeded that of normal nuclei from the same block was also calculated (5C exceeding rate). Stage and grade provided independent prognostic information. Aneuploidy was associated with higher mortality but neither ploidy nor 5C exceeding rate were prognostic indicators. Image analysis is a useful and accurate method for ploidy determination and provides additional data on DNA quantitation but this information is not predictive of the clinical outcome.

Adult↗
PubMed1991

Soft tissue and visceral sarcomas in Irish patients. A preliminary report from the Dublin Soft Tissue Tumour Panel.

Sarcomas of the soft tissues and viscera are a diverse group of uncommon neoplasms that often present difficult diagnostic and management problems. The Dublin Soft Tissue Tumour Panel prospectively reviewed pathology material from 137 patients of four Dublin teaching hospitals between January 1989 and August 1990. The prevalence of sarcomas in Irish patients was found to be similar to that estimated for the United States. The most common sarcoma of soft tissues was malignant fibrous histiocytoma (14) and the most common visceral sarcoma was leiomyosarcoma (10). The most problematic diagnoses were 3 peripheral neuroepitheliomas (extraskeletal Ewing's sarcomas) which occurred in patients aged 19-27 years, distinctly younger than the typical adult sarcoma patient. Clinical follow-up is in progress and will be combined with the findings of a linked retrospective study, to facilitate evaluation of all aspects of management.

Abdominal Neoplasms↗
PubMed1991

Improved wound healing with a modified electrosurgical electrode.

Previous studies comparing standard electrosurgical (ES) electrode and steel scalpel (SS) wound healing have reported poor initial tensile strength, a delay in reaching maximum tensile strength and an increased inflammatory response in the ES wounds. The hypothesis that a smaller needle (modified) electrode would give better wound healing than a standard electrode was tested. Using histology as a parameter of wound healing, incisions created by a modified electrode, a standard electrode and a steel scalpel were compared. Sixty Sha Sha mice were divided into 10 groups. Standardised dorsal skin incisions were made using steel scalpel, standard and modified electrosurgical cutting electrodes. Mice were sacrificed on days 0, 1, 2, 3, 5, 7, 9, 14, 28 and 42. The incised skin was processed for standard and immunohistochemical staining. The standard ES wound had significantly higher numbers of polymorphonuclear leukocytes in comparison to the SS and modified ES wounds (p less than or equal to 0.01). However, macrophage numbers were found to be significantly lower in the ES wounds when compared to the SS wounds on days two and five (p less than or equal to 0.05). The fibroblast response was delayed by up to two days in the ES wounds when compared to the SS wounds. Epithelialisation was completed by day two in the SS and modified ES groups but was only complete by day three in the standard ES group (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Adenosquamous carcinoma of the prostate: a case report.

Mixed types of carcinoma of the prostate are rare. The majority of those described (22 cases) are examples of mixed adenocarcinoma and transitional cell carcinoma. Much more unusual is the mixed adenosquamous carcinoma, of which only three cases have been described. This report presents an additional case of the rare adenosquamous carcinoma of the prostate. It discusses the clinicopathologic features and the possible histogenesis of this tumor and suggests a role for stilbestrol in its development.

Adenocarcinoma↗