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Biomedical subjects

M D Walsh

Publications and source records attributed to M D Walsh.

At least 55 records · Page 3Linked to original sources
PubMed1995

Prognostic significance of MUC1 epithelial mucin expression in breast cancer.

The epithelial mucin produced by the MUC1 gene is present in the apical cell membrane of normal breast epithelial cells and is highly expressed in many breast cancers. Several studies have provided conflicting evidence regarding the relationship between MUC1 expression and survival in breast cancer patients. In this study a detailed immunohistological analysis of MUC1 expression was performed using monoclonal antibody BC2 and was related to other tumor characteristics and patient survival. Patients whose tumors showed MUC1 expression in greater than 75% of tumor cells had significantly poorer disease-free and overall survival (P < .05). The proportion of cells showing cytoplasmic MUC1 expression was prognostically significant, but the proportion of cells that lined gland spaces showing apical membrane staining was of no prognostic significance. A high level of MUC1 expression was significantly associated with the presence of axillary node metastases and estrogen receptors but not with other tumor characteristics.

Analysis of Variance↗
PubMed1994

Mucin expression by transitional cell carcinomas of the bladder.

OBJECTIVE: To examine the presence of a membrane-associated and secreted mucin (MUC1) and a secreted gel-forming mucin (MUC2) in normal and malignant urothelium. MATERIALS AND METHODS: Sections were obtained from archival paraffin blocks from 11 patients with nonmalignant urological conditions and 89 patients with transitional cell carcinomas (TCC). Mucin expression was examined by immunohistochemistry using monoclonal antibodies BC2 and 4F1, reactive with epitopes on the protein core of MUC1 and MUC2 respectively. RESULTS: In normal urothelium MUC1 was limited predominantly to the apical membranes of the umbrella cell layer. MUC1 was present in all cases of TCC, and the pattern of expression divided into three categories: luminal membrane staining only, luminal plus cytoplasmic staining of intermediate +/- basal layers, or staining of only isolated cells or cell groups. These staining patterns were significantly associated with both tumour grade and stage (P < 0.001), with cytoplasmic staining more prevalent in higher grade and stage tumours. MUC2 was not detected in normal urothelium, and was present in 40% of cases of TCC, characterized by intense granular cytoplasmic staining. No association between MUC2 expression and either tumour grade or stage was demonstrated. CONCLUSION: MUC1 mucin was expressed by both normal and malignant urothelium, with increased expression characteristic of higher grade and stage tumours. MUC2 expression was found in 40% of tumours but not in normal urothelium. The role of these mucins in the biology of the bladder requires further investigation.

Aged↗
PubMed1994

Immunohistological expression of p53 in primary pT1 transitional cell bladder cancer in relation to tumour progression.

OBJECTIVE: To determine whether p53 expression is a marker of tumour progression in superficially invasive (pT1) transitional cell carcinoma of the bladder. PATIENTS AND METHODS: The immunohistochemical status of the p53 protein in 28 pT1 primary bladder cancers was determined on frozen tissue and archival paraffin block sections using three primary antibodies (CM-1, PAB1801 and D07). The findings were compared with the patients' progress. All the patients, except for those who died during the course of the study, were followed up by check cystoscopy for a minimum of 2 years. RESULTS: Immediately adjacent frozen sections stained identically in 10 of 16 cases for CM-1 and PAB1801. For paraffin sections, identical staining patterns were seen for PAB1801 and D07 in 21 of 26 sections. However, inter- and intra-tumour staining for p53 was very variable, even with the same antibody. The heterogeneity of p53 positive cell distribution in the tumours indicates potential for significant sampling errors if random sections are chosen as representative of p53 status. CONCLUSION: The p53 status of the primary tumours did not relate to patient outcome. The results obtained do not support the use of immunohistological p53 expression as a discriminating prognostic indicator in pT1 transitional cell carcinoma of the bladder.

Biomarkers, Tumor↗
PubMed1993

The adverse effect of fibrin-clot inhibiting drugs on intravesical bacillus Calmette-Guérin efficacy for superficial bladder cancer.

Bacillus Calmette-Guérin (BCG) is currently thought to act as a biological immune modifier in effecting antitumour activity. Recent evidence suggests that BCG binding to fibronectin (FN), a tissue glycoprotein, may be a prerequisite step in initiating this response. Drugs inhibiting the availability of exposed FN in the bladder after urothelial disruption may adversely affect the efficacy of BCG. Data are presented of 45 patients with tumour limited to mucosa (pTa) or carcinoma in situ (CIS) given intravesical BCG therapy, with (group 1) or without (group 2) fibrin clot-inhibiting drugs concurrently during treatment. The success rate of 11.1% for group 1 (1/9) patients was significantly less than that of 69.4% for group 2 (25/36), (chi 2 = 7.79, P < 0.01 Fisher's exact test) supporting the suggestion that the concurrent administration of fibrin-clot inhibiting drugs may adversely affect the outcome of BCG therapy.

Administration, Intravesical↗
PubMed1993

Expression of MUC2 epithelial mucin in breast carcinoma.

AIMS: To examine the expression of the MUC2 epithelial mucin in breast carcinoma; to relate this to patient survival. METHODS: Sections from 210 breast carcinomas were stained with the anti-MUC2 core protein monoclonal antibody, 4F1, using an immunoperoxidase technique. The proportion of tumour cells positively stained and the localisation and intensity of any staining were recorded. Expression of MUC2 was compared with histological type and grade, tumour size, presence of nodal metastases, presence of oestrogen receptors, and menopausal status. The prognostic value of MUC2 expression was examined using Kaplan-Meier survival analysis. RESULTS: MUC2 mucin was detected in 19% of cases of invasive carcinoma, in 11% of cases of carcinoma in situ, where present, but very rarely in adjacent normal breast epithelium. Presence of MUC2 was significantly associated with a shorter disease free interval (p < 0.05), although the observed difference in duration of overall survival was not significant. CONCLUSIONS: The MUC2 detected in breast carcinoma may be underglycosylated or staining may represent detection of the protein core before the completion of glycosylation. The virtual absence of 4F1 reactivity in normal breast epithelium suggests that, unlike the MUC1 mucin, the MUC2 mucin is not highly expressed by these cells. The mechanism by which expression of MUC2 affects the biology of breast tumours is unclear, although expression may be a reflection of general derepression of genes during tumour progression.

Biomarkers, Tumor↗
PubMed1992

An immunohistological demonstration of c-erbB-2 oncoprotein expression in primary urothelial bladder cancer.

Sections of formalin-fixed, paraffin-blocked tissue from 116 primary transitional cell carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining of cell membranes, known to correlate with gene amplification, was seen in 22 (19%) of the 116, with variable staining from tumour to tumour and within tumours themselves. Consistent with its mooted value as a prognosticator in bladder cancer, the c-erbB-2 oncoprotein was detected in 13 (of 40) grade III and 9 of the 26 muscle-invasive tumours examined compared to 1 (of 25) grade I and 6 (of 66) mucosa only (pTa) lesions. These results support further examination of c-erbB-2 expression in bladder cancer.

Aged↗
PubMed1991

Intestinal transferrin receptors and iron absorption in the neonatal rat.

The transferrin receptor is a major protein found on the basolateral membranes of intestinal epithelial cells, yet its possible role in intestinal iron metabolism and also in iron absorption is unclear. We have studied intestinal transferrin receptor expression during the peri- and postnatal development of the small intestine of the rat using immunohistochemistry with a monoclonal antibody to the rat receptor. Two major changes in transferrin receptor expression in the developing small intestine were found, a decrease in receptor expression associated with birth, and an increase at the time of weaning. Around the time of weaning there was a large decrease in iron absorption, but there was no direct correlation between absorption and transferrin receptor expression. However, at both birth and weaning there were major changes in intestinal cell kinetics, and the distribution of receptor correlated well with the distribution of proliferating cell populations. In addition, as the intestinal epithelial cells differentiated and stopped dividing, there was a redistribution of transferrin receptors from the cell surface to intracellular sites. These data suggest that the most likely role of the transferrin receptor in the neonatal intestine is in the supply of iron to the developing epithelial cells in the crypts, and that the receptor does not play a direct role in iron transit across the intestinal epithelium.

Aging↗
PubMed1991

A comparison of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene expression in head and neck squamous cell carcinomas.

The proto-oncogenes c-erbB-2 and epidermal growth factor (EGF) receptor which encode 2 closely homologous transmembrane glycoproteins have been found amplified and/or overexpressed in a range of epithelial malignancies. In a series of 46 head and neck squamous cell cancers (SCCs), immunohistochemical reactivity for the EGF receptor was detected in all cases, particularly at the invading edge of cellular islands of SCC and in the basal cells of normal adjacent squamous epithelium. Southern blot analysis demonstrated EGF receptor gene amplification in 3 cases. In contrast, strong membrane staining for the c-erbB-2 oncoprotein was not detected in any sample, and there were no cases of c-erbB-2 gene amplification. Despite a close structural and (presumed) functional homology between these 2 receptor-oncoproteins in the development of malignancy, we report that their expression in SCCs is markedly different. Furthermore, unlike the situation for breast cancer, quantitation of the c-erbB-2 or EGF receptor oncoproteins is unlikely to yield important prognostic information in this group of patients.

Adult↗
PubMed1990

Transferrin receptor expression in primary superficial human bladder tumours identifies patients who develop recurrences.

A group of 65 patients with superficial bladder carcinoma was followed for 2 years and tumour recurrence rate was correlated both with transferrin receptor status of the initial primary tumour and with the results of voided urine cytology. Nine of 24 patients with transferrin receptor negative tumours had recurrences compared with 30 of 41 patients with transferrin receptor positive tumours. This difference was highly significant. Urine cytology at presentation was also predictive of further tumour formation: of 30 patients who were transferrin receptor positive and had positive urine cytology, 25 developed recurrences.

Adult↗
PubMed1989

An immunohistological examination of inflammatory cell infiltration in primary testicular seminomas.

Inflammatory cell infiltration was characterized in five classical seminomatous testicular tumours using immunohistochemical techniques. These cells of immunological lineage were sited mostly around vessels. Lymphocytes were the most numerous, T cells outnumbering B cells in all sections studied. The helper/inducer subgroup predominated in the T cell family with suppressor cells more common than cytotoxic cells. Plasma cells constituted only a small percentage of this population as did natural killer cells. No Langerhans cells were identified. Phagocytic macrophages were twice as common as antigen-presenting macrophages yet T lymphocytes were 15 times more common than these antigen-presenting macrophages.

Antibodies, Monoclonal↗
PubMed1988

An immunohistopathological characterisation of mixed non-seminomatous germ cell tumors.

Immunohistological techniques were used to characterise inflammatory cell infiltrates in mixed germ cell tumours. The distribution of these infiltrates was much more variable than in pure seminomas but could not be related accurately to any particular tumour type. There were approximately equal numbers of B and T cells in these areas and helper/inducer T cells were more common than suppressor/cytotoxic lymphocytes. Within these areas of inflammatory cells, the subtype composition was similar to that seen in pure seminomas.

B-Lymphocytes↗
PubMed1987

Transferrin receptor expression by human bladder transitional cell carcinomas.

The expression of transferrin receptors (TFR) by normal and neoplastic urothelial cells was studied in "control" patients and in patients with transitional cell carcinoma of the bladder. These tumours were graded independently and consisted of 19 grade I, 30 grade II and 19 grade III lesions. TFRs were identified using a monoclonal antibody specific for TFR (OKT9) in an immunofluorescent or avidin/biotin-immunoperoxidase technique on fresh frozen sections. TFRs were not detected on normal urothelium. However, positive staining was found to increase with increasing pathological grade and stage of the tumours, ranging from 31.6% of grade I to 78.9% of grade III tumours and 51.2% of pTa (mucosa only lesions) to 87.5% of pT2/pT2+ (muscle invasion +/- deeper) primary urothelial malignancies.

Adult↗