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Niall O'Higgins

Publications and source records attributed to Niall O'Higgins.

At least 19 recordsLinked to original sources
PubMed2007

Lipophilin B: A gene preferentially expressed in breast tissue and upregulated in breast cancer.

Lipophilin B (LPB), which is also known as BU101, is a secretoglobin which exists in vivo as a complex with the mammary-specific protein, mammaglobin A (MGA). The aim of our study was to investigate the expression of LPB in a panel of breast and nonbreast tissues and compare its expression with that of MGA. Using RT-PCR, LPB mRNA was detected in 16/25 (64%) of normal breast specimens, 23/30 (77%) of fibroadenomas, 102/156 (65%) of primary breast cancers and in 8/36 (22%) nonbreast tissues. Levels of expression of LPB mRNA were significantly higher in breast cancers compared to both normal breast tissues (p = 0.02) and nonbreast tissue (p < 0.001). In the primary breast cancers, expression of LPB mRNA was positively correlated with the estrogen receptor (p = 0.045) but inversely related to both tumor grade (p < 0.001) and proliferation rates (p = 0.0345). Compared to MGA, expression of LPB was more sensitive but less specific for breast cancer. Using Western blotting, LPB migrated with an approximate molecular mass of 7-8 kDa, the expected molecular mass of free LPB. Immunohistochemical analysis of breast cancers showed that LPB expression was predominantly confined to the cytoplasm of tumor cells. We conclude that expression of LPB is preferentially but not exclusively restricted to breast tissue. Since LPB was expressed relatively specifically in breast tissue and was significantly upregulated in breast carcinomas, it is a promising candidate biomarker for breast cancer.

Biomarkers, Tumor↗
PubMed2006

Predictive value of breast lesions of "uncertain malignant potential" and "suspicious for malignancy" determined by needle core biopsy.

BACKGROUND: The optimum management of patients whose needle core biopsy (NCB) results are of "uncertain malignant potential" (B3) or "suspicious for malignancy" (B4) is unclear. This study correlates B3 and B4 NCB findings with excision histology to determine associated rates of malignancy. METHODS: All NCBs categorized as B3 or B4 were identified from a series of 3729 NCBs. Results of biopsies were reported as normal/nondiagnostic (B1), benign (B2), uncertain malignant potential (B3), suspicious but not diagnostic of malignancy (B4), or malignant (B5) according to the B classification system. B3 lesions included atypical intraductal epithelial proliferations (AIEPs), lobular neoplasia, papillary lesions, radial scars, and potential phyllodes tumors. Histological concordance between NCB and excision specimen was analyzed. RESULTS: A total of 211 B3 lesions and 51 B4 lesions were identified during the study period. The open biopsy rate after a B3/B4 finding was 86% (n = 226). The overall rate of malignancy for B3 lesions after excision was 21%. The B3 lesion-specific rates of malignancy were 6% for radial scars, 14% for papillomas, 35% for AIEP, and 44% for lobular neoplasia. Of the patients with a B4 categorization, 90% (44 of 49) were diagnosed with carcinoma after surgery. Those that were "suspicious for ductal carcinoma-in-situ" and "suspicious for invasion" correlated accurately with excision findings in 81% and 89% of patients, respectively. CONCLUSIONS: Management of lesions in the B3 categorization must be tailored to the patient because the specific lesion types are associated with highly variable rates of malignancy. A repeat biopsy or a therapeutic wide local excision should be undertaken in lesions with a B4 NCB categorization because such lesions are associated with a particularly high risk of malignancy at excision.

Biopsy, Needle↗
PubMed2006

The role of major duct excision and microdochectomy in the detection of breast carcinoma.

BACKGROUND: The association of nipple discharge with breast carcinoma has resulted in numerous women undergoing exploratory surgery to exclude malignancy. The aim of this study was to determine whether pre-operative factors can identify those patients that are most at risk of carcinoma. METHODS: All patients over a 14-year period (1991-2005) who had a microdochectomy or subareolar exploration for the evaluation of nipple discharge were assessed. Patient characteristics, pre-operative imaging and pathological findings were analysed. RESULTS: Of the 211 patients included in this study, 116 patients had pathological (unilateral, uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with pathological discharge and 2.4% (n = 2) of patients with non-pathological discharge were diagnosed with carcinoma. Overall, major duct excision resulted in the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in 39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 111) of patients. In the patients determined to have malignancy, 44% (n = 4) were premenopausal. No patient with a non-bloody discharge in the total population analysed (28%; n = 59/211), or in the population with a pathological discharge (21%; n = 24/116) was found to have carcinoma upon excision. CONCLUSION: Microdochectomy or major duct excision performed for nipple discharge resulted in a low rate of malignancy on excision. Conservative management of non-bloody nipple discharge can be considered in patients with no other clinical or radiological signs of malignancy.

Adult↗
PubMed2006

Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only.

BACKGROUND AND OBJECTIVES: Ductal carcinoma in-situ on core biopsy does not preclude invasive disease within the excision specimen, resulting in the need for further axillary surgery. We sought to identify predictors of invasion when DCIS is present on core biopsy. METHODS: From a database of 895 breast cancer patients, patients with DCIS on core biopsy who had subsequent surgical excision were identified. Their excision pathology and preoperative mammography were correlated with risk of invasion. RESULTS: Patients (93) with a preoperative diagnosis of DCIS on core biopsy were identified. On excision, 31 patients (33%) had invasive carcinoma and 13 patients (14%) had microinvasion. A preoperative finding of calcification only on mammogram was associated with DCIS on excision (P = 0.014), whereas the presence of other mammographic features increased the risk of invasion. Size > or =5 cm on excision pathology was associated with increased risk of invasion (P = 0.002). Forty-eight percent (n = 11/23) of those diagnosed by ultrasound-guided core biopsy had frank invasion on excision compared to 21% (n = 12/57) diagnosed by stereotactic techniques (P = 0.017). CONCLUSION: Mammographic features and tumor size can help predict invasion in patients who have DCIS on core biopsy. Patients who have features other than calcification on mammography or have tumor size > or =5 cm should be considered for a sentinel node biopsy.

Biopsy↗
PubMed2006

A pathologic assessment of adequate margin status in breast-conserving therapy.

BACKGROUND: The definition of a clear margin in breast-conserving therapy is uncertain. The purpose of this study was to correlate the tumor-margin distance of the excision specimen with the presence of residual tumor at reoperation. We also analyzed predictors of compromised margins and of residual disease. METHODS: All patients who underwent breast-conserving therapy for invasive disease from 1999 to 2003 were reviewed. Pathologic characteristics and the precise tumor distance from the radial margin were recorded. A radial margin was compromised if invasive or (ductal) in situ carcinoma was <5 mm from the margin. RESULTS: Of the 612 patients who underwent breast conservation, 211 (34%) had compromised margins, and 39 had undetermined margins. Of the 161 patients who had a reoperation for compromised margins, 87 (54%) had residual disease. Residual disease after reoperation was present in 58% (56 of 96), 56% (9 of 16), and 45% (22 of 49) of those with tumor-margin distances <1 mm, > or =1 and <2 mm, and > or =2 and <5 mm, respectively. There was a progressive decline in residual disease for each millimeter until a rate of 22% for tumor-margin distances of > or =4 mm and <5 mm was reached. Pathologic size (P = .004), an extensive intraductal component (P = .002), referral from a symptomatic rather than a population-based screening program (P = .02), and the absence of a preoperative diagnosis by core biopsy (P < .0001) were predictive of compromised margins. Only young age (<45 years) was predictive of finding residual disease on reoperation (P = .02). CONCLUSIONS: A total of 45% of patients who had tumor 2 to 5 mm from the radial margin had residual disease on reoperation. Our results support a policy of requiring a 5-mm margin in patients undergoing breast-conserving therapy for invasive disease.

Breast Neoplasms↗
PubMed2006

Identifying patients at risk of compromised margins following breast conservation for lobular carcinoma.

BACKGROUND: The association of invasive lobular carcinoma with high rates of compromised margins in breast conservation makes choice of operation for these patients difficult. We sought to identify patients at risk of compromised margins following breast conservation surgery. METHODS: We reviewed all patients with invasive lobular and invasive ductal carcinoma over a 5-year period (1999-2004). The imaging, pathology and surgical details of patients with invasive lobular carcinoma undergoing breast conservation were analyzed. RESULTS: A total of 991 patients with invasive ductal carcinoma and 150 patients with invasive lobular carcinoma were identified. Lobular carcinomas had a compromised margin rate of 49% (n = 38/77) in breast conservation compared to 24% (n = 143/588) of ductal carcinomas (P < .0001). Mammographic size (P = .017), pathological size (P = .01), age (P = .03), multifocality (P < .0001), and lymphovascular invasion (P = .015) were significantly associated with compromised margins. CONCLUSION: Invasive lobular carcinoma has a 49% rate of compromised margins following breast conservation. Mammographic size greater than 1.5 cm and young age were preoperative factors predictive of compromised margins.

Breast Neoplasms↗
PubMed2006

Needle core biopsy in the diagnosis of phyllodes neoplasm.

BACKGROUND: Accurate identification of phyllodes neoplasms without surgical intervention is difficult, reducing the ability to manage "benign" lumps non-operatively and impacting on the open benign biopsy rate. Needle core biopsy is considered to be a highly accurate technique in the diagnosis of breast carcinoma. Its accuracy in the diagnosis of phyllodes neoplasm has not been established. METHODS: A series of 3729 core biopsies performed between January 1999 and July 2005 were examined. All core biopsies followed by surgical excision were identified. Histologic concordance between core biopsy and excision specimen was analyzed. RESULTS: Twenty-three patients had phyllodes neoplasm on excisional biopsy with prior core biopsy findings as follows: phyllodes neoplasm (n=2), "equivocal" for phyllodes neoplasm (n=12), fibroadenoma (n=3), benign (n=6). The false negative rate for phyllodes neoplasm was therefore 39% (n=9/23). Of the total biopsy series, 35 patients had a core biopsy suggesting the possibility of phyllodes neoplasm. Of these, 32% (n=11) were found to be phyllodes neoplasm on excision, 3% (n=1) phyllodes neoplasm with breast carcinoma, 6% (n=2) breast carcinoma, and 3% (n=1) sarcoma. When a preference for phyllodes neoplasm (n=4) was stated on the equivocal core biopsies, excision correlated with the stated preference; this correlation also occurred in 90% (n=9/10) of core biopsies where fibroadenoma was favored. CONCLUSIONS: Needle core biopsy rarely produces a definite preoperative diagnosis of phyllodes neoplasm. A diagnosis of fibroadenoma or equivocal phyllodes neoplasm on core biopsy should not prevent excision if clinical suspicion remains.

Adult↗
PubMed2005

Mammaglobin a in breast cancer: existence of multiple molecular forms.

Existing serum-based markers for breast cancer all lack organ specificity. Mammaglobin A (MGA) is a 93 amino acid protein expressed almost exclusively in breast tissue. The aim of our study was to investigate the different forms of MGA protein in fibroadenomas and breast carcinomas. MGA protein was measured by Western blotting in 132 breast cancers, 29 fibroadenomas and 14 nonbreast tissues. MGA protein in breast tissue was found to exist in 2 main forms. These forms migrated with approximate molecular masses of 18 and 25 kDa. Both forms of MGA were detected more frequently in breast carcinomas compared to fibroadenomas. The high molecular weight form of MGA but not the low molecular weight form was found more frequently in hormone receptor-positive than in receptor-negative cancers. Furthermore, an inverse relationship was found between the high molecular weight form of MGA and both tumour grade and proliferation index. No significant correlation was found between the MGA proteins and either tumor size or nodal status. Our results show that MGA protein exists in 2 main forms in breast tissue. As the high molecular weight form correlated positively with hormone receptors and negatively with tumor grade and proliferation rate, its presence is likely to be associated with a favourable prognosis for breast cancer. As expression of MGA is almost breast specific, it is a promising marker for breast cancer. Its most immediate use is likely to be in detecting micrometastases from breast cancer.

Biomarkers, Tumor↗
PubMed2005

Unusual presentation of a giant parathyroid adenoma: report of a case.

Parathyroid adenomas account for most cases of primary hyperparathyroidism (1 degrees HPT). Certain symptoms and biochemical abnormalities alert the surgeon to their presence, since these benign tumors are rarely evident on physical examination. Moreover, because they are usually very small, preoperative localization using sestamibi scanning or ultrasonography is required to avoid bilateral neck exploration. Parathyroid adenomas rarely attain huge proportions. We report a case of a parathyroid adenoma measuring 8 x 5 x 3.5 cm and weighing 110 g; to our knowledge the greatest mass reported in the literature. Interestingly, despite its huge size it did not cause many of the hypercalcemic symptoms usually associated with larger adenomas, but rather it manifested with symptoms of local pressure, another unusual property of this atypical tumor.

Adenoma↗
PubMed2005

The accuracy of ultrasound, stereotactic, and clinical core biopsies in the diagnosis of breast cancer, with an analysis of false-negative cases.

OBJECTIVE: Preoperative core biopsy in breast cancer is becoming the standard of care. The aim of this study was to analyze the various methods of core biopsy with respect to diagnostic accuracy and to examine the management and outcome of those patients with false-negative biopsies. METHODS: All patients undergoing core biopsy for breast abnormalities over a 5-year period (1999-2003) were reviewed. The accuracy rates for each method of core biopsy, the histologic agreement between the core pathology and subsequent excision pathology, and the length of follow-up for cases of benign disease were studied. Patients whose biopsies were benign but who were subsequently diagnosed with cancer underwent detailed review. RESULTS: There were 2427 core biopsies performed over the 5-year period, resulting in a final diagnosis of cancer in 1384 patients, benign disease in 954 patients, and atypical disease in 89 patients. Biopsy type consisted of 1279 ultrasound-guided cores, 739 clinically guided cores, and 409 stereotactic-guided cores. The overall false-negative rate was 6.1%, with specific rates for ultrasound-, clinical-, and stereotactic-guided cores of 1.7%, 13%, and 8.9%, respectively. False-negative biopsies occurred in 85 patients, and in 8 of these patients the diagnosis was delayed by greater than 2 months. In all other false-negative cases, "triple assessment" review allowed prompt recognition of discordant biopsy results and further evaluation. CONCLUSION: Ultrasound guidance should be used to perform core biopsies in evaluating all breast abnormalities visible on ultrasound. Adherence to principles of triple assessment following biopsy allows for early recognition of the majority of false-negative cases.

Adult↗
PubMed2004

High preoperative CA 15-3 concentrations predict adverse outcome in node-negative and node-positive breast cancer: study of 600 patients with histologically confirmed breast cancer.

BACKGROUND: CA 15-3 is the most widely used serum marker in breast cancer. Currently, its main uses are in the surveillance of patients with diagnosed disease and monitoring the treatment of patients with advanced disease. METHODS: Preoperative CA 15-3 concentrations were measured prospectively in 600 patients with histologically confirmed breast cancer. Marker concentrations were related to patient outcome by both univariate and multivariate analysis. RESULTS: After a median follow-up of 6.27 years, patients with high preoperative concentrations of CA 15-3 (>30 units/L) had a significantly shorter overall survival pattern than those with low concentrations. As a prognostic factor, CA 15-3 was independent of tumor size, axillary node status, and patient age. As well as being prognostic in the total population of patients, CA 15-3 also predicted outcome in different subgroups of patients, including those with both node-negative and node-positive disease, those who were both estrogen receptor (ER)-negative and ER-positive, and those younger and older that 50 years of age. CA 15-3 was also predictive of outcome irrespective of the type of adjuvant therapy administered, i.e., whether adjuvant hormone therapy, adjuvant chemotherapy, or radiotherapy was administered. CONCLUSION: Assay of CA 15-3 is a relatively inexpensive, convenient, and noninvasive method for evaluating prognosis in newly diagnosed breast cancer patients.

Adult↗
PubMed2004

Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.

BACKGROUND: Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated. MATERIALS AND METHODS: Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody. RESULTS: Plasma endostatin levels, in breast cancer patients, were significantly elevated (P = 0.015) in the post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76 etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival. CONCLUSIONS: Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.

Adult↗
PubMed2003

Expression of ADAM-9 mRNA and protein in human breast cancer.

The ADAMs (a disintegrin and metalloprotease) are membrane proteins containing both protease and adhesion domains and thus may be potentially important in cancer invasion and metastasis. The aim of our study was to investigate the distribution and potential clinical significance of ADAM-9 in breast cancer. ADAM-9 expression was measured using both reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. ADAM-9 mRNA was expressed more frequently in both breast carcinomas (72/110, 66%) and fibroadenomas (21/38, 55%) compared to normal breast tissue (6/25, 24%) (p = 0.0004, p = 0.028, respectively). Multiple forms of ADAM-9 protein were detected by Western blotting, i.e., at 124, 84 and 48 kDa under reducing conditions and at 115, 76, 55, 52 and 46 kDa under nonreducing conditions. The 84 and 55 kDa forms were detected more frequently in the primary cancers compared to normal breast tissue (p < 0.0001, p = 0.0002, respectively). In addition, relative levels of the 84 kDa mature form were significantly higher in the primary cancers than in the fibroadenomas (p = 0.003), while the reverse was found for the 124 kDa precursor form (p = 0.026). In the carcinomas, the 84 kDa form of ADAM-9 protein was expressed at higher levels in node-positive than node-negative cancers (p = 0.05) and correlated positively with HER-2/neu protein levels (r = 0.313, p = 0.016). This is the first report to describe expression of any ADAM in a large number of human carcinomas.

ADAM Proteins↗
PubMed2003

Caspase 3 in breast cancer.

PURPOSE: An inability to undergo apoptosis is widely thought to contribute to both tumorigenesis and tumor progression. One of the key mediators of apoptosis is the thiol protease caspase 3. In this investigation, caspase 3 mRNA and protein expression in breast cancer was examined. EXPERIMENTAL DESIGN: Caspase 3 was measured at the mRNA level using reverse transcription-PCR and at the protein level using both Western blotting and activity assays. Levels of apoptosis were determined using an ELISA, which detects nucleosomes released during DNA fragmentation. RESULTS: Relative levels of caspase 3 mRNA were similar in breast carcinomas (n = 103), fibroadenomas (n = 25), and normal breast tissues (n = 6). However, levels of both the precursor and active forms of caspase 3 were significantly higher in carcinomas compared with both fibroadenomas (P = 0.0188) and normal breast tissues (P = 0.0002). Levels of apoptosis were also highest in the carcinomas and correlated significantly with active caspase 3 levels (r = 0.481; P = 0.0003). In the carcinomas, expression of caspase 3 showed no significant relationship with either tumor size, tumor grade, nodal status, or steroid receptor status but was significantly higher in ductal carcinomas than in lobular carcinomas (P = 0.0188). CONCLUSIONS: We conclude that rates of apoptosis as measured by both caspase 3 activation and nucleosome release are higher in breast cancer than in nonmalignant breast tissue. This finding would appear to conflict with the widely held belief that apoptosis is reduced in malignancy. The proliferation:apoptosis ratio, however, may be higher in carcinomas than in the corresponding normal tissue.

Apoptosis↗