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N O'Higgins

Publications and source records attributed to N O'Higgins.

At least 19 recordsLinked to original sources
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

Ets2 transcription factor in normal and neoplastic human breast tissue.

The Ets family of transcription factors regulate the expression of multiple genes involved in tumour formation and progression. The aim of this work was to test the hypothesis that the expression of Ets2 in breast cancers was associated with parameters of tumour progression and metastasis. Using reverse-transcriptase polymerase chain reaction (RT-PCR), Ets2 mRNA was detected in 69% of 181 breast carcinomas, 63% of 43 fibroadenomas and 47% of 43 specimens of normal breast tissue. Levels were significantly higher in carcinomas compared with normal breast tissue (P = 0.006). Using Western blotting, Ets2 protein was found to migrate as two bands with molecular masses of 52 kDa (p52) and 54kDa (p54). Levels of both proteins were significantly higher in the carcinomas compared with both fibroadenomas (P = 0.0001) and normal breast tissue (P = 0.0001). In the carcinomas, a significant relationship was found between the p52 and p54 form of Ets2 (r = 0.51, P < 0.0001; Spearman correlation). Also, in the carcinomas, a significant correlation was found between both forms of Ets2 protein and urokinase plasminogen activator (uPA) (for p52, r = 0.43, P = 0.0005, n = 68; for p54, r = 0.50, P = 0.0001, n = 68). As Ets2 binding sites are present on the uPA promoter, Ets2 may be one of the transcription factors regulating uPA expression in human breast cancer.

Blotting, Western↗
PubMed2005

Expression of survivin and its splice variants survivin-2B and survivin-DeltaEx3 in breast cancer.

Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cancer and axillary nodal metastases. Survivin, survivin-2B and survivin-DeltaEx3 mRNA were measured using semiquantitative RT-PCR. In the primary carcinomas, we related mRNA for each form of survivin to both survivin protein and apoptosis. For each type of breast tissue, survivin was the predominant form detected, being present in 146 out of 156 (93.6%) primary breast carcinomas, 11 out of 11 (100%) axillary nodal metastases, 21 out of 31 (67.7%) fibroadenomas and five out of 22 (22.7%) specimens of normal breast tissue. Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P < 0.0001). Levels of both survivin-2B and survivin-DeltaEx3 but not survivin were significantly higher in nodal metastases than primary carcinomas. Survivin mRNA levels correlated significantly with survivin protein. Finally, both survivin and survivin-DeltaEx3 but not survivin-2B correlated positively with apoptosis. Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin. Our results suggest that the different forms of survivin may have different roles in apoptosis in breast cancer.

Alternative Splicing↗
PubMed2005

Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration.

The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis, while high levels of tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were measured in patients with benign (n=103) and malignant breast disease (n=113) by immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen levels of tPA and tPA-PAI-1 complex were significantly higher in patients with breast carcinoma compared to the control group. In plasma from the breast cancer patients, uPA levels correlated weakly but significantly with those of tPA (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no significant correlation was found between plasma and tumor tissue levels of uPA, PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that determination of these factors in plasma do not reflect their concentration in tumor tissue. Therefore, measurement of PA components in blood cannot be recommended for assessing prognosis in breast cancer.

Biomarkers, Tumor↗
PubMed2004

Overexpression of the Ets-1 transcription factor in human breast cancer.

The Ets family of transcription factors regulate expression of multiple genes involved in tumour progression. The aim of this study was to investigate the expression of Ets-1 in a large panel of human breast cancers and relate its levels to the parameters of tumour progression and metastasis. Using RT-PCR, Ets-1 mRNA was detected in 30 out of 42 (71%) fibroadenomas and 131 out of 179 (73%) primary breast carcinomas. Similarly, levels of Ets-1 mRNA were not significantly different in fibroadenomas and primary breast carcinomas. Using Western blotting, four forms of the Ets-1 protein were detected, that is, p33, p42, p51 and p52. Levels of both p51 and p52 but not p33 and p42 were present at significantly higher levels in the carcinomas compared to the fibroadenomas (for p51, P<0.007; for p52, P<0.02; Mann-Whitney U-test). Levels of p52, p51 and p33 correlated significantly with uPA protein levels (P<0.01), while only levels of p52 correlated significantly with HER-2/neu protein levels (P<0.01). Using immunohistochemistry, Ets-1 was found predominantly in tumour cells, but was also detected in some stromal cells surrounding tumour islands. We conclude that, while at the mRNA level, Ets-1 was found at similar levels in fibroadenomas and primary breast carcinomas, higher protein levels were detected in the cancers compared to the benign specimens. Since p52, p51 and p33 correlate with uPA levels, these forms of Ets-1 may play a role in breast cancer metastasis.

Biomarkers, Tumor↗
PubMed2004

Bone sialoprotein-coated femoral implants are osteoinductive but mechanically compromised.

Aseptic loosening of femoral implants in total hip replacement remains an unsolved orthopaedic problem. This paper investigates the potential role of bone sialoprotein (BSP) in enhancing bone-implant adherence. As BSP is osteoinductive in rat calvarial models, we investigated whether BSP is similarly osteoinductive when coated onto intramedullary femoral implants. BSP-coated titanium implants were implanted into the femur of female 'Wistar' rats (average weight 215 g) that were sacrificed at days 10, 20 and 30. Harvested femoral implants were subjected to pullout testing and then examined histologically. BSP-coated implants demonstrate osteoinduction when examined histologically. Plugging the femoral canal with BSP prior to inserting the implant neither increased implant pullout strengths nor further increased osteoblastic activity. This study has demonstrated for the first time that BSP is osteoinductive when coated onto femoral implants and inserted into bones subjected to mechanical loading. However, we found that pullout strengths are a function of implant surface topographical characteristics and are not affected by BSP coating or histological osteoinduction.

Animals↗
PubMed2004

Needle-localised biopsy of impalpable breast lesions: a novel adjunct to surgical technique and specimen mammography.

Successful screening programmes have resulted in the more frequent detection of early impalpable breast tumours. Effective surgical management of impalpable lesions demands a precise approach to excision which is currently aided by radiologically guided needle-localisation of the lesion prior to operative removal. The surgical specimen procured is most commonly evaluated for tumour presence by specimen mammography intra-operatively or by histological analysis. The latter is more accurate but requires lengthy laboratory processing, which may result in re-operation if the primary excision is inadequate. Although advocated as the standard of care, specimen mammography remains an imperfect technique. In this article we describe a piece of surgical apparatus which attempts to address some of the concerns associated with specimen mammography. It is an inexpensive compression device which reduces operative time, avoids portable fluoroscopy, increased radiation and the necessity for specialised equipment

Biopsy, Needle↗
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

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

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

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗
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↗
PubMed2001

The European Society of Surgical Oncology.

Surgery is the key to local tumor control and survival in the vast majority of cancer patients. Optimally performed oncological operations, based both on a profound knowledge of the disease and on organ-based technical expertise are therefore essential. In this field the multinational European Society of Surgical Oncology (ESSO) wants to play a pivotal role, improving surgical treatment and encouraging and promoting education and training in surgical oncology at all levels. To achieve this goal the ESSO is of the opinion that recognition of surgical oncology as a separate subspecialty has to pursued.

Accreditation↗
PubMed2001

Evolving structures in surgical oncology and the role of the Federation of European Cancer Societies in continuing medical education.

This article describes the evolution of a European system of accreditation of educational events in oncology and the establishment by the Federation of European Cancer Societies of the Accreditation Council of Oncology in Europe. It draws attention to the need for a coordinated system which is acceptable in the different European countries so that an international system of "Eurocredits" can be devised. Through the official Union Europeénne des Médecins Specialistes (UEMS), reciprocity with the accrediting bodies in the United States and other countries is planned.

Accreditation↗
PubMed2000

Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix. Currently, at least 19 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high levels of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours

Apoptosis↗