Biomedical subjects

E W McDermott

Publications and source records attributed to E W McDermott.

At least 19 recordsLinked to original sources

PubMed2006

A positive role for PEA3 in HER2-mediated breast tumour progression.

Overexpression of HER2 is associated with an adverse prognosis in breast cancer. Despite this, the mechanism of its transcriptional regulation remains poorly understood. PEA3, a MAP kinase (MAPK)-activated member of the Ets transcription factor family has been implicated in the transcriptional regulation of HER2. The direction of its modulation remains controversial. We assessed relative levels of PEA3 expression and DNA binding in primary breast cultures derived from patient tumours (n=18) in the presence of an activated MAPK pathway using Western blotting and shift analysis. Expression of PEA3 in breast tumours from patients of known HER2 status (n=107) was examined by immunohistochemistry. In primary breast cancer cell cultures, growth factors induced interaction between PEA3 and its DNA response element. Upregulation of PEA3 expression in the presence of growth factors associated with HER2 positivity and axillary lymph node metastasis (P=0.034 and 0.049, respectively). PEA3 expression in breast cancer tissue associated with reduced disease-free survival (P<0.001), Grade III tumours (P<0.0001) and axillary lymph node metastasis (P=0.026). Co-expression of PEA3 and HER2 significantly associated with rate of recurrence compared to patients who expressed HER2 alone (P=0.0039). These data support a positive role for PEA3 in HER2-mediated oncogenesis in breast cancer.

Axilla↗

PubMed2006

Diagnostic accuracy of core biopsy for ductal carcinoma in situ and its implications for surgical practice.

BACKGROUND: Core biopsy is considered to be a highly accurate method of gaining a preoperative histological diagnosis of breast cancer. Ductal carcinoma in situ (DCIS) is often impalpable and is a more subtle form of breast cancer. AIM: To investigate the accuracy of core biopsy in the diagnosis of cancer in patients with DCIS. METHODS: All patients who had invasive cancer (n = 959) or DCIS (n = 92) that was confirmed by excision between 1999 and 2004 were identified. The diagnostic methods, histology of the core biopsy specimen and excision histology were reviewed in detail. RESULTS: Core biopsy was attempted in 88% (81/92) of patients with DCIS and in 91% (874/959) of those with invasive disease. Of those patients who underwent core biopsy, a diagnosis of carcinoma on the initial core was made in 65% (53/81) of patients with DCIS compared with 92% (800/874) of patients with invasive disease (p<0.0001). Smaller lesion size (p = 0.005) and lower grade (p = 0.03) were associated with increased risk for a negative or non-diagnostic core in patients with DCIS. The nature of the mammographic lesion or the method of biopsy did not affect the probability of an accurate core biopsy. Patients who had a preoperative diagnosis of DCIS by core biopsy had a reoperation rate of 36% compared with 65% of those that did not have a preoperative diagnosis (p = 0.007). CONCLUSION: Although core biopsies are highly accurate forms of obtaining a preoperative diagnosis in patients with invasive breast cancer, this is not the case in DCIS. As the number of surgical procedures can be reduced by core biopsy, it is still of considerable value in the management of DCIS.

Biopsy↗

PubMed2005

Meralgia paraesthetica following open appendicectomy.

Meralgia paraesthetica is a painful condition attributed to entrapment or injury to the lateral femoral cutaneous nerve. It has been described following operations which could result in direct injury to the nerve such as iliac crest bone harvesting. It has also been reported following surgery remote from the nerve. Following open appendicectomy injury may occur following direct trauma to an anatomical variant of this nerve, which can occur in up to 25% of the population. We report two cases that became clinically evident immediately following open appendicectomy with subsequent confirmatory electromyography studies. Meralgia paraesthetica following open appendicectomy has not been reported in the medical literature. This is an under-recognised complication of open appendicectomy. Management can be challenging for patient and clinician.

Adult↗

PubMed2004

Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine-resistant breast cancer.

The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-alpha and ER-beta. Although ER-alpha has been well characterized, the role of ER-beta as a prognostic indicator remains unresolved. To determine isoform-specific expression of ER and coexpression with activator proteins, we examined the expression and localisation of ER-alpha, ER-beta and the coactivator protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and immunofluorescence in a cohort of human breast cancer patients (n=150). Relative levels of SRC-1 in primary breast cultures derived from patient tumours in the presence of beta-oestradiol and tamoxifen was assessed using Western blotting (n=14). Oestrogen receptor-beta protein expression was associated with disease-free survival (DFS) and inversely associated with the expression of HER2 (P=0.0008 and P<0.0001, respectively), whereas SRC-1 was negatively associated with DFS and positively correlated with HER2 (P<0.0001 and P<0.0001, respectively). Steroid receptor coactivator 1 protein expression was regulated in response to beta-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-beta and SRC-1 was inversely associated (P=0.0001). The association of ER-beta protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer.

Adult↗

PubMed2004

Positron emission tomography in the staging and management of breast cancer.

BACKGROUND: Breast cancer is the commonest cause of cancer death in women in the Western world, and imaging is essential in its diagnosis and staging. Metabolic imaging is a novel approach to improving the detection of cancers, as malignant transformation of cells is often associated with increased metabolic activity. This review assesses the possible role of positron emission tomography (PET) as a single non-invasive imaging modality to replace or complement current imaging and surgical practices in the diagnosis and staging of breast cancer. METHODS AND RESULTS: A Medline search was performed and articles were cross-referenced with other relevant material. Evaluation of primary breast cancer with PET has shown a sensitivity of between 64 and 100 per cent and a specificity of 33-100 per cent; diagnostic accuracy appears to be related to tumour size. Difficulties arise in altered fluorodeoxyglucose uptake in lobular carcinoma, carcinoma in situ and benign inflammatory breast disease. In axillary staging, sensitivities of between 25 and 100 per cent have been reported, but with a false-negative of up to 20 per cent. In the assessment of distant metastasis and asymptomatic patients with raised levels of tumour markers, PET was superior to conventional imaging modalities. CONCLUSION: PET is not a single diagnostic and staging tool that can replace current surgical, histological and radiological staging. Its main role in breast cancer lies in the investigation of metastatic disease and the evaluation of pathological response to various chemotherapeutic regimens.

Axilla↗

PubMed2004

Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1.

BACKGROUND: In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth factor induced mitogen activated protein kinase activity can phosphorylate not only the oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1. AIM: To determine whether insensitivity to endocrine treatment in HER2 positive patients is associated with enhanced expression of coactivator proteins, expression of the HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1, was assessed in a cohort of patients with breast cancer of known HER2 status. METHODS: PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of known HER2 status (HER2 positive, n = 35) and six reduction mammoplasties was assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1 was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was correlated with clinicopathological parameters. RESULTS: In primary breast tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p = 0.0486, p = 0.0444, and p = 0.0012, respectively). In the HER2 positive population, PEA3 expression was associated with SRC-1 (p = 0.0354), and both PEA3 and SRC-1 were significantly associated with recurrence on univariate analysis (p = 0.0345; p<0.0001). On multivariate analysis, SRC-1 was significantly associated with disease recurrence in HER2 positive patients (p = 0.0066). CONCLUSION: Patients with high expression of HER2 in combination with SRC-1 have a greater probability of recurrence on endocrine treatment compared with those who are HER2 positive but SRC-1 negative. SRC-1 may be an important predictive indicator and therapeutic target in breast cancer.

Adult↗

PubMed2004

Factors affecting metastases to non-sentinel lymph nodes in breast cancer.

AIMS: Because sentinel lymph node (SLN) biopsy for breast cancer has become well established, one of the challenges now is to determine which patients require a completion axillary dissection following a positive SLN biopsy. METHODS: A prospective database of patients who underwent SLN biopsy for invasive breast cancer from July 1999 to November 2002 (n = 180) was analysed. Fifty four patients (30%) had one or more positive SLN, and all underwent a completion axillary dissection. This subgroup was further analysed to delineate which factors predicted non-SLN metastasis. RESULTS: Twenty six of the 54 patients with a positive SLN had additional metastases in non-SLNs. Significant variables that predicted non-SLN metastasis included extranodal extension (odds ratio (OR), 17.399; 95% confidence interval (CI), 1.69 to 178.96) and macrometastasis within the SLN (OR, 6.985; 95% CI, 1.291 to 37.785). CONCLUSIONS: In patients with invasive breast cancer and a positive SLN, extranodal extension or macrometastasis within the SLN were both independent predictors of non-SLN involvement.

Adult↗

PubMed2004

Surgical intervention in screen-detected patients versus symptomatic patients with breast cancer.

OBJECTIVES: The impact of population-based screening for breast cancer on the rate of breast-conserving surgery has not been established. We sought to evaluate whether surgical intervention in patients with screen-detected breast cancer differed from those with clinically detected tumours. SETTINGS: St Vincent's University Hospital and the BreastCheck Merrion Unit, part of the Irish National Breast Screening Programme, were the setting for the study. METHODS: A total of 902 patients referred for surgery to St Vincent's University Hospital over a four-year period (2000-2003) were studied. Patients with breast cancers detected during the prevalent round of screening (n=325) were compared with patients presenting with symptomatic disease (n=577). The operative procedure, nature of axillary surgery and histopathological findings were recorded in each case. RESULTS: There was an increase in breast-conserving therapy in the screened population compared with symptomatic cases (68% screened versus 53% symptomatic; p<0.0001), with a corresponding reduction in axillary clearance rates (65% screened versus 81% symptomatic; p<0.0001). Nodal positivity was similar following correction for size in all tumours >1 cm, regardless of method of detection. Sentinel node biopsy was successfully undertaken in 39% of tumours <2 cm (T1 tumours) [corrected] in the screening population. CONCLUSIONS: The screened population was statistically more likely to have breast-conserving therapy than the symptomatic group. Sentinel node biopsy has evolved into an acceptable alternative to axillary clearance in T1 cancers, particularly in screen-detected cases.

Axilla↗

PubMed2003

Prognostic importance of survivin in breast cancer.

Survivin is a member of the inhibitor of apoptosis (IAP) family, and is also involved in the regulation of cell division. Survivin is widely expressed in foetal tissues and in human cancers, but generally not in normal adult tissue. This study examined the expression of surviving protein in a series of 293 cases of invasive primary breast carcinoma. Survivin immunoreactivity was assessed using two different polyclonal antibodies, and evaluated semiquantitatively according to the percentage of cells demonstrating distinct nuclear and/or diffuse cytoplasmic staining. Overall, 60% of tumours were positive for survivin: 31% demonstrated nuclear staining only, 13% cytoplasmic only, and 16% of tumour cells demonstrated both nuclear and cytoplasmic staining. Statistical analysis revealed that survivin expression was independent of patient's age, tumour size, histological grade, nodal status, and oestrogen receptor status. In multivariate analysis, nuclear survivin expression was a significant independent prognostic indicator of favourable outcome both in relapse-free and overall survival (P<0.001 and P=0.01, respectively). In conclusion, our results show that survivin is frequently overexpressed in primary breast cancer. Nuclear expression is most common and is an independent prognostic indicator of good prognosis.

Adult↗

PubMed2003

Elevated expression and altered processing of fibulin-1 protein in human breast cancer.

The extracellular matrix protein fibulin-1 suppresses the motility and invasiveness of a variety of tumour cell types in vitro as well as the growth of fibrosarcoma tumours in nude mice. In this study, fibulin-1 protein expression in breast carcinoma specimens and normal breast tissue was evaluated immunohistologically. Fibulin-1 protein expression was also semiquantitatively assessed by immunoblot analysis in a collection of normal breast tissues (n=18), benign tumours (n=5) and breast carcinomas (n=39). In normal breast tissue, fibulin-1 protein expression predominated in the ductal epithelium and underlying myoepithelium, with weaker staining evident in the loose connective surrounding the ducts. Examination of breast carcinomas revealed that the tumour cells also expressed fibulin-1 protein. The level of mature fibulin-1 polypeptide (100 kDa) was higher in the breast carcinoma specimens as compared to normal breast tissue (Mann-Whitney U-test, P=0.0005). In addition to the mature fibulin-1 polypeptide, several smaller sized polypeptides of 55, 50 and 25 kDa were detected using monoclonal antibodies reactive towards an epitope located at the N-terminus of fibulin-1. The immunoreactive 50 kDa polypeptide was detected more frequently in breast carcinoma specimens than in normal breast tissue (chi(2)=17.22, P<0.0001). Furthermore, the ratio of the 50 kDa fragment to the mature fibulin-1 polypeptide correlated with the level of oestrogen receptor alpha (Spearman correlation coefficient, rs=0.49, P<0.003, n=36) and progesterone receptor (rs=0.43, P=0.008, n=36) expression in the tumour specimens. Taken together, these findings indicate that elevated expression and altered processing of fibulin-1 is associated with human breast cancer.

Antibodies, Monoclonal↗

PubMed2003

The prevention of breast cancer.

BACKGROUND: Despite advances in the early detection and treatment of breast carcinoma, the mortality and morbidity rates associated with this disease remain high. Primary prevention, therefore, offers the best chance of making a major impact on outcome. METHODS: The aim was to review the rationale, current stage of development and adverse effects of the strategies involved in the primary prevention of breast carcinoma. A review of the literature was undertaken by searching the MEDLINE database for the period 1966-2002 without language restrictions. RESULTS AND CONCLUSION: Currently, the only agent to have general approval for chemoprevention of breast carcinoma is tamoxifen. Women who derive the greatest benefit in terms of risk reduction from tamoxifen are premenopausal with a 5-year Gail risk factor of more than 1.66 per cent, postmenopausal with a 5-year Gail risk factor of more than 3 per cent, and postmenopausal without a uterus. In these specific subgroups, tamoxifen should be considered for the chemoprevention of breast carcinoma. Raloxifene, retinoids, aromatase inhibitors and cyclo-oxygenase 2 inhibitors require further clinical investigation before adoption in this context. Surgical intervention should largely be limited to those women who have a BRCA1 or BRCA2 mutation.

Antineoplastic Agents, Hormonal↗

PubMed2003

Lack of prognostic effect of Cox-2 expression in primary breast cancer on short-term follow-up.

AIMS: Cyclo-oxygenase (Cox) catalyses the conversion of arachidonic acid into prostaglandins (PG) and other eciosanoids. The prostaglandins, especially PGE(2) are implicated in tumorigenesis via angiogenesis and suppression of immune reactivity. There are two known isoforms of the enzyme, Cox-1, which is constitutively expressed and the inducible isoform, Cox-2. Cox-2 is induced in response to inflammatory mediators, growth factors, oncogenes and mitogens. Non-selective Cox inhibitors may reduce the relative risk of colonic and breast carcinoma. METHODS: We studied the expression of Cox-2 by immunohistochemistry in 106 primary breast carcinoma specimens collected over a three-year period, using a commercially available polyclonal antibody on formalin-fixed, paraffin-embedded tissue. The slides were examined independently by two pathologists. Tumours were classified according to accepted criteria and an immunohistochemical score (IHS) was calculated for each specimen. The IHS combines the percentage of immunoreactive cells (quantity score) and an estimate of staining intensity (staining intensity score). RESULTS: All patients were female. The mean age was 53 years, range 28-86 years. Forty percent (n=42) of tumours were node negative and 60% (n=64) node positive. Forty-nine percent (n=52) of tumours were grade 3, a further 49% (n=52) grade 2 and 2% (n=2) grade 1. There was no statistically significant correlation between IHS and tumour size, grade, histology, nodal status, estrogen receptor or progesterone receptor positivity. A trend was observed showing an IHS of zero is associated with prolonged survival compared with an IHS of 9-12. CONCLUSION: Cox-2 expression in primary breast cancer does not correlate with accepted pathological or biochemical prognostic indicators.

Adult↗

PubMed2003

Intradermal radioisotope injection optimises sentinel lymph node identification in breast cancer.

AIM: Currently there is no consensus on the optimal technique for sentinel lymph node (SLN) identification in patients with breast cancer. The aim was to compare the efficacy of intraparenchymal and intradermal isotope injection in sentinel lymph node mapping for breast cancer. METHODS: One hundred and twenty-five patients with histologically confirmed invasive breast cancer underwent SLN mapping using radioisotope and isosulphan blue dye followed by a back-up axillary dissection. The first 80 patients had intraparenchymal (IP) injection of radioisotope given in four portions around the tumor. The remaining 45 patients had an intradermal (ID) injection given at a single site over the tumour. Both groups had isosulphan blue dye injected around the tumour. Sentinel node(s) were identified using a combination of lymphoscintigraphy, blue dye and an intra-operative hand held gamma probe. RESULTS: The preoperative lymphoscintigram (LSG) demonstrated a SLN significantly more often in the ID isotope group compared to the IP isotope group (P=0.002). A combination of blue dye and isotope successfully located the SLN in 96% of the intraparenchymal group and 100% of the intradermal group. CONCLUSION: Our results suggest that intradermal isotope injection in combination with intraparenchymal blue dye optimises the localization of the sentinel lymph node in breast cancer.

Axilla↗

PubMed2003

The role of molecular staging in malignant melanoma.

AIMS: To review the role of tyrosinase RT-PCR in the detection of clinically occult metastatic disease, both within the regional lymph nodes and peripheral blood of patients with malignant melanoma. Secondly, to assess whether the detection of such minimal disease has clinical implications for patients with melanoma. METHODS: A review of the literature was undertaken by searching the MEDLINE database for the period 1966-2002 without any language restrictions. Keywords included 'Molecular staging of melanoma', 'Reverse transcription polymerase chain reaction', 'Malignant melanoma' and 'Tyrosinase'. CONCLUSIONS: Detection of tyrosinase RT-PCR positive cells within the peripheral blood correlates with the clinical stage of malignant melanoma, the primary tumour thickness and other known prognostic indicators. Positive tyrosinase RT-PCR is associated with a reduction of disease-free survival and overall survival. Current studies demonstrate a higher rate of recurrence in RT-PCR positive patients with clinical stage II and III disease. Implications of a positive result within the regional lymph nodes are less well defined. A significant correlation has been demonstrated between positive results and increasing primary melanoma thickness. However, a large number of false-positive results have been demonstrated, due to benign naevi and schwann cells, which may hamper any statistically significant conclusions being reached.

Clinical Trials as Topic↗

PubMed2003

Objective measurement of breast cancer oestrogen receptor status through digital image analysis.

AIMS: The authors have previously described quantitative, computer-assisted analysis of oestrogen receptor status in immuno-histochemically stained sections in patients with primary breast cancer. The aim of this study was to validate the aforementioned system against the commonly used methods of assessing oestrogen receptor status. METHODS: Paraffin embedded sections from 156 patients with primary breast carcinoma were stained with anti-alpha-oestrogen receptor monoclonal antibody (1D5) using a standard immunohistochemical protocol. Images from 10 high-powered fields were captured from each section using a digital camera mounted on a microscope and analyzed using Adobe Photoshop image analysis software. A nuclear mask was obtained by digitally selecting the nuclear area. Staining intensity in the nuclear mask was then analyzed using red-scale absorption characteristics. Manual assessment of oestrogen receptor status was performed through counting the percentages of cells that are positive from 200 randomly sampled nuclei from ten high powered fields HPF. Cut off value for positivity was taken as 10%. Cytosolic oestrogen receptor concentration was measured through enzyme immunisation. Cut off value for ER positivity was taken as 200 fmol/g (wet tissue). RESULTS: One hundred and fifty-six sections were studied of which 41 were ER negative. Median percentage positivity in the remainder was 90% (17-100) by manual assessment. The median red scale value was 108 (58-156). A close correlation was observed between median optical density of the nuclear mask and percentage positivity assessed manually (P<0.0001). There was a significant correlation between the optical density of the nuclear mask and cytosolic oestrogen receptor concentration (P<0.001). CONCLUSION: Oestrogen receptor positivity can be accurately assessed through digital image analysis. This process offers objective data regarding the amount of oestrogen receptors within the nuclei as well as the percentage of nuclei, which express oestrogen receptors.

Adult↗

PubMed2003

Percutaneous endoscopic gastrostomy: 5 years of clinical experience on 238 patients.

Since Percutaneous Endoscopic Gastrostomy (PEG) feeding was introduced, 20 years ago it has been increasingly utilised in medical practice. The aim of this study was to assess the current indications and complications associated with PEG feeding. This study was a retrospective review of hospital charts dealing with PEG placement over a period of five years. The indications for insertion were, central nervous disease 76% (n = 156), other benign disease 14% (n = 28) and malignancy 10% (n = 21). Cerebrovascular accidents (CVA) alone accounted for 47% (n = 97). Ninety seven (50%) patients had minor complications, which included 43 (22%) wound infections. There were 6 (3%) major complications, including peritonitis, perforation and aspiration pneumonia. There were four deaths (2%) related to PEG placement, of whom three developed aspiration pneumonia and one peritonitis. The overall 30 day mortality rate was 16%. There was a 75% increase in the use of PEG placement over the five year period. PEG placements were associated with a 53% morbidity and a 2% procedure related mortality. There was a 16% 30 day mortality following PEG placement suggesting that the selection criteria for PEG placement may need to be refined further.

Adolescent↗

PubMed2002

Pregnancy-associated breast cancer.

Twelve premenopausal women diagnosed with pregnancy-associated breast cancer between May 1985 and October 1999 were reviewed. Three patients were diagnosed in the first trimester of pregnancy, five in the second trimester, and three during the third trimester. There was one patient who was five weeks postpartum. At the time of diagnosis nine patients had lymph node involvement and two of these had metastatic disease. Four patients received primary chemotherapy. The remainder had surgery. Five patients died, two had metastatic disease at time of diagnosis, median survival was 31 months. There were three fetal deaths, one termination and two during primary chemotherapy. The diagnosis of breast cancer during pregnancy is difficult. Presentation is usually at an advanced stage. Surgery can be safely performed during pregnancy and adjuvant chemotherapy should not be postponed until after delivery.

Adult↗

PubMed2002

Parathyroid localisation--current practice.

In patients with primary hyperparathyroidism, neck exploration by an experienced parathyroid surgeon is curative in excess of 95% of cases. Considerable efforts have been devoted to improving parathyroid imaging. New radionucleotide agents and scanning procedures have markedly improved the success rate of localization studies with subsequent development of minimally invasive surgical techniques. In this article we review the different localization techniques and their current role in parathyroid surgery for primary hyperparathyroidism

Humans↗