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Biomedical subjects

E W Kay

Publications and source records attributed to E W Kay.

48 records · Page 3Linked to original sources
PubMed1996

Inter-observer variation of p53 immunohistochemistry--an assessment of a practical problem and comparison with other studies.

The aims of this study were to analyse the expression of p53 by immunohistochemistry in a range of malignant and pre-malignant conditions and to assess the degree of inter-observer variability in interpretation of p53 immunostaining. Formalin-fixed paraffin-embedded sections from 28 colorectal carcinomas (CRC), 40 cervical intraepithelial neoplasia lesions (CIN), 22 transitional cell carcinomas of the bladder (TCC), 10 invasive squamous carcinomas of uterine cervix and 21 squamous cell carcinomas of skin were examined. A polyclonal antibody was used in 90 cases. A monoclonal antibody was used in the remainder. Ten cases were stained with both. Aberrant expression of p53 protein was documented in 48% of squamous cell carcinomas of skin, 29% of CRC, 22% of CIN and 23% of TCC. All cases of squamous cell carcinoma of uterine cervix were negative. Inter-observer variation occurred in 7% of cases examined. This was confined to two tumour groups, TCC and CIN. Our results showed that p53 oncoprotein expression by immunohistochemistry was identified in 26% of cases but the range was wide (0-48%) and appeared to be tumour specific. Inter-observer variability in the interpretation of immunohistochemical staining was low (7%) and was restricted to two tumour groups.

Biomarkers, Tumor↗
PubMed1996

Evaluation of p53 protein expression in renal cell carcinoma: comparison of two antibodies.

The aims of this study were to establish a profile for the expression of p53 in primary renal cell carcinoma using the polyclonal antibody NCL-CB1 and the monoclonal antibody D07, and to compare the results of staining with both antibodies. Ninety-six cases were studied using formalin-fixed paraffin-embedded tissue. Positive nuclear staining ranged from 5% (D07) to 12% (NCL-CM1). Positive cytoplasmic staining ranged from 7% (D07) to 25% (NCL-CM1) of cases. Interobserver agreement was excellent. The findings suggest that such a low level of immunohistochemical positivity reduces any potential prognostic value for p53 in this tumour type.

Antibodies↗
PubMed1995

The pathology of cervical cancer.

The significant changes over the last decade in the CIN/cervical carcinoma area have involved the increasing recognition of many cervical carcinomas as adenocarcinomas, rather than squamous cell type, and their propensity for arising in young women. Another area of interest is the deployment of new molecular techniques that are unveiling the role of oncogene co-factors (e.g. HPV, p53) in the biologic evolution of CIN and hopefully glandular dysplasia.

Adenocarcinoma↗
PubMed1995

ras and p53 in the prediction of survival in Dukes' stage B colorectal carcinoma.

Aims-To determine possible associations between p53 allelic deletion, c-Ki-ras mutational activation, immunohistochemical detection of p53 and ras proteins, various clinicopathological variables, and patient outcome in 168 Dukes' stage B colorectal carcinomas.Methods-Allelic deletion at the p53 tumour suppressor gene locus was detected using polymerase chain reaction (PCR) based loss of heterozygosity (LOH) assays. Overexpressed proteins were detected using the CM1 polyclonal antibody. A PCR based assay was used to detect the presence of activating mutations at codon 12 of c-Ki-ras. Immunostaining was carried out using a monoclonal antibody to p21(ras).Results-p53 LOH, CM1 immunostaining, c-Ki-ras mutational activation, and p21(ras) immunostaining were not predictive of survival by logrank analysis. Multivariate analysis using Cox regression did not predict survival in this group of tumours.Conclusions-Aberrations in ras and p53 are unlikely to play an important role in the subdivision of patients with Dukes' stage B colorectal carcinoma into more accurate prognostic strata. It is possible that later genetic events are more important in conferring a specific phenotype on the resultant Dukes' stage B tumour.

Journal Article↗
PubMed1994

Soft tissue and visceral sarcomas in Irish patients. Interim analysis of data obtained by the Dublin Soft Tissue Tumour Panel.

The Dublin Soft Tissue Sarcoma Panel was established in 1989 with a view to achieving a unified approach to diagnosis and management of soft tissue and visceral sarcomas. This interim report presents data on 265 prospectively-evaluated patients and on a separate retrospective series of 126 patients. The patients in the prospective series were treated by 93 different surgical and medical specialists. Tumours presented in all anatomic sites and ranged in size from 0.2 to 60 cm. Leiomyosarcoma was the commonest tumour type. Eighty-nine tumours were inoperable at clinical presentation. There was a consensus panel diagnosis in over 90%, non-neoplastic reactive lesions and primitive round cell tumours being the most difficult cases diagnostically. Management, including onward referral for chemotherapy or radiation therapy, was inconsistent. The 2-year survival figures were: 43% (1989-91) and 37% (1980-88). These findings should provide a basis for the evaluation of coherent treatment strategies for Irish sarcoma patients.

Adolescent↗
PubMed1994

Cytoplasmic c-erbB-2 protein expression correlates with survival in Dukes' B colorectal carcinoma.

The prognostic significance of c-erbB-2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty-four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c-erbB-2 staining was seen in 55 cancers (33.5%). Cytoplasmic staining was unrelated to patient age (P = 0.31), sex (P = 0.69), tumour site (P = 0.69), size (P = 0.57), histological grade (P = 0.42) or ploidy status (P = 0.21) but was found more frequently in obstructing cancers (P = 0.03). Mean follow up of the patient population was 6.3 years. Five-year-survival estimated by the Kaplan-Meier life-table method was 47% for those with cytoplasmic c-erbB-2 staining and 77% for those without (log rank analysis; P < or = 0.0001). Stepwise regression analysis identified c-erbB-2 staining (relative risk, 2.51; P = 0.0005) and bowel obstruction (relative risk, 1.99; P = 0.015) as independent predictors of survival. It is suggested that cytoplasmic c-erbB-2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer.

Aged↗
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↗
PubMed1991

Acute and chronic bioeffects of single and multiple doses of piezoelectric shockwaves (EDAP LT.01).

Piezoelectric second generation lithotriptors are an established means of administering extracorporeal shockwave lithotripsy (ESWL) enabling treatment to be performed without anaesthesia or analgesia, but higher shockwave doses and multiple or staged treatment are frequently required. The bioeffects of this modality of ESWL, therefore, require further assessment. Seven experimental groups of adult male rabbits were treated using the EDAP LT.01 in order to determine the acute and chronic bioeffects of clinical dose, excess dose, divided excess dose, high frequency and multiple treatment (X10) piezoelectric shockwaves (PSW). Renal function was measured before and after treatment using mercaptoacetyltriglycine (MAG 3) scans. Gross and histological morphological changes were assessed at one and 30 days following application of PSW. Application of single clinical dose PSW was not associated with any significant functional or morphological renal injury. Excess dose PSW caused transient gross renal contusion, which resolved in the majority of animals with no persistent microscopic abnormality. Divided excess dose PSW resulted in no gross or microscopic damage. High frequency PSW was associated with mild histological abnormality. Multiple PSW treatments caused small discrete fibrotic lesions in all cases, without any change in renal function.

Animals↗
PubMed1991

Bleeding due to colorectal atheroembolism. Diagnosis by biopsy of adenomatous polyps or of ischemic ulcer.

Atheroembolism, although not infrequent at autopsy, is seldom identified in life, when it may present as a multisystem disease involving lower limbs, kidney, and gastrointestinal (GI) tract. Diagnosis of isolated GI involvement usually requires examination of surgically resected tissue, because recognition by endoscopic GI biopsy is exceptional. We diagnosed colorectal atheroembolism by biopsy in four patients. All were elderly (68-80 years old) and had generalized atheroma, including aortic aneurysms. Three patients had sudden onset of frank rectal bleeding with clots or bloody diarrhea, lower abdominal discomfort, and tenderness. Biopsy revealed atheroemboli in a rectal ischemic ulcer and in colorectal adenomatous polyps. In all three, disease resolved on conservative management and did not recur during the period of follow-up. In the fourth patient, asymptomatic atheroembolism was identified in an adenomatous polyp at the splenic flexure. Extraintestinal disease attributable to atheroembolism was not present in any of the patients. Atheroembolism with manifestations confined to the colon may sometimes be diagnosed by biopsy, appears to be more frequent than currently recognized, and may present a diagnostic challenge as a self-limited episode of rectal bleeding.

Aged↗
PubMedDate not supplied

Primary lymphoma of the bladder: a report of three cases.

BACKGROUND: Primary lymphoma of the bladder is rare and its management is an evolving field. AIMS: To highlight primary lymphoma of the bladder as a possible diagnosis in cases of bladder neoplasm and to illustrate the currently favoured management options. METHODS: Three cases of primary bladder lymphoma are reported and management is reviewed. RESULTS: Each of the three cases was managed differently with each management approach yielding a favourable outcome. CONCLUSION: Chemotherapy combined, if necessary, with surgery or radiation therapy, should be the standard of care, depending on the full histological diagnosis.

Aged↗