46 results on '"Carder PJ"'
Search Results
2. A little bit more on the slide
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Carder, PJ and Liston, JC
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Clinical pathology -- Research -- Health aspects -- Analysis -- Methods ,Medical tests -- Analysis -- Methods -- Health aspects -- Research ,Biopsy -- Methods -- Analysis -- Health aspects -- Research ,Breast cancer -- Health aspects -- Prevention -- Diagnosis -- Research ,Medical screening -- Methods -- Health aspects -- Analysis -- Research ,Health ,Diagnosis ,Prevention ,Analysis ,Research ,Methods ,Health aspects - Abstract
In 2001-2, 89% of cancers detected by the UK National Health Service Breast Screening Programme (NHSBSP) were diagnosed preoperatively. (1) In 1996-7, the figure was 63%. Year on year increases [...]
- Published
- 2003
3. An audit of benign biopsies performed in patients assessed by the Leeds/Wakefield Breast Screening Unit
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Carder, PJ, primary and Liston, JC, additional
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- 2002
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4. Mutation of the p53 gene precedes aneuploid clonal divergence in colorectal carcinoma
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Carder, PJ, primary, Cripps, KJ, additional, Morris, R, additional, Collins, S, additional, White, S, additional, Bird, CC, additional, and Wyllie, AH, additional
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- 1995
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5. Oestrogen receptor beta: what it means for patients with breast cancer.
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Speirs V, Carder PJ, Lane S, Dodwell D, Lansdown MRJ, Hanby AM, Speirs, Valerie, Carder, Pauline J, Lane, Sally, Dodwell, David, Lansdown, Mark R J, and Hanby, Andrew M
- Abstract
Oestrogen receptor (ER) alpha is a well established prognostic marker in breast cancer, and all patients who are ER alpha positive receive tamoxifen as adjuvant endocrine therapy. Although ER alpha predicts a favourable disease outcome, the usefulness of ER beta as a clinical prognostic marker remains to be defined. Here, we outline the history of both ERs and discuss the implications ER beta has to patients with breast cancer. [ABSTRACT FROM AUTHOR]
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- 2004
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6. Pleomorphic LCIS what do we know? A UK multicenter audit of pleomorphic lobular carcinoma in situ.
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Masannat YA, Husain E, Roylance R, Heys SD, Carder PJ, Ali H, Maurice Y, Pinder SE, Sawyer E, and Shaaban AM
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- Adult, Age Factors, Aged, Aged, 80 and over, Biopsy, Breast pathology, Breast Carcinoma In Situ chemistry, Breast Carcinoma In Situ ultrastructure, Breast Neoplasms chemistry, Breast Neoplasms ultrastructure, Carcinoma, Lobular chemistry, Female, Humans, Medical Audit, Middle Aged, Neoplasm Grading, Neoplasm Invasiveness, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Retrospective Studies, United Kingdom, Breast Carcinoma In Situ pathology, Breast Neoplasms pathology, Carcinoma, Lobular pathology
- Abstract
Aims: Pleomorphic lobular carcinoma in situ (PLCIS) is a relatively newly described pathological lesion that is distinguished from classical LCIS by its large pleomorphic nuclei. The lesion is uncommon and its appropriate management has been debated. The aim of this study is to review data from a large series of PLCIS to examine its natural history in order to guide management plans., Materials and Methods: Comprehensive pathology data were collected from two cohorts; one from a UK multicentre audit and the other a series of PLCIS cases identified from within the GLACIER study cohort. 179 cases were identified of whom 176 had enough data for analysis., Results: Out of these 176 cases, 130 had invasive disease associated with PLCIS, the majority being of lobular type (classical and/or pleomorphic). A high incidence of histological grade 2 and 3 invasive cancers was noted with a predominance of ER positive and HER-2 negative malignancy. When PLCIS was the most significant finding on diagnostic biopsy the upgrade to invasive disease on excision was 31.8%, which is higher than pooled data for classical LCIS and DCIS., Conclusion: The older age at presentation, high grade of upgrade to invasive cancer, common association with higher grade tumours suggest that PLCIS is an aggressive form of insitu disease. These findings support the view that PLCIS is a more aggressive form of lobular in situ neoplasia and supports the tendency to treat akin to DCIS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
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- 2018
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7. Accuracy of classification of invasive lobular carcinoma on needle core biopsy of the breast.
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Naidoo K, Beardsley B, Carder PJ, Deb R, Fish D, Girling A, Hales S, Howe M, Wastall LM, Lane S, Lee AH, Philippidou M, Quinn C, Stephenson T, and Pinder SE
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- Biopsy, Large-Core Needle, Breast pathology, Breast Neoplasms classification, Breast Neoplasms diagnostic imaging, Carcinoma, Lobular classification, Carcinoma, Lobular diagnostic imaging, Diagnostic Errors, Female, Humans, Ireland, Magnetic Resonance Imaging, Neoplasm Invasiveness, Reproducibility of Results, United Kingdom, Breast Neoplasms pathology, Carcinoma, Lobular pathology
- Abstract
Although the UK National Institute for Health and Care Excellence guidelines recommend that in patients with biopsy-proven invasive lobular carcinoma (ILC), preoperative MRI scan is considered, the accuracy of diagnosis of ILC in core biopsy of the breast has not been previously investigated. Eleven pathology laboratories from the UK and Ireland submitted data on 1112 cases interpreted as showing features of ILC, or mixed ILC and IDC/no special type (NST)/other tumour type, on needle core biopsy through retrieval of histology reports. Of the total 1112 cases, 844 were shown to be pure ILC on surgical excision, 154 were mixed ILC plus another type (invariably ductal/NST) and 113 were shown to be ductal/NST. Of those lesions categorised as pure ILC on core, 93% had an element of ILC correctly identified in the core biopsy sample and could be considered concordant. Of cores diagnosed as mixed ILC plus another type on core, complete agreement between core and excision was 46%, with 27% cases of pure ILC, whilst 26% non-concordant. These data indicate that there is not a large excess of expensive MRIs being performed as a result of miscategorisation histologically., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
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- 2016
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8. Updated UK Recommendations for HER2 assessment in breast cancer.
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Rakha EA, Pinder SE, Bartlett JM, Ibrahim M, Starczynski J, Carder PJ, Provenzano E, Hanby A, Hales S, Lee AH, and Ellis IO
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- Antineoplastic Agents therapeutic use, Benchmarking, Biomarkers, Tumor genetics, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Female, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence standards, Molecular Targeted Therapy, Patient Selection, Precision Medicine, Predictive Value of Tests, Quality Control, Quality Indicators, Health Care standards, Receptor, ErbB-2 antagonists & inhibitors, Receptor, ErbB-2 genetics, Specimen Handling standards, United Kingdom, Workflow, Workload standards, Biomarkers, Tumor analysis, Breast Neoplasms enzymology, Immunohistochemistry standards, In Situ Hybridization standards, Receptor, ErbB-2 analysis
- Abstract
Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and false-negative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status. In situ hybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence of HER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
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- 2015
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9. Conservative management of screen-detected radial scars: role of mammotome excision.
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Rajan S, Wason AM, and Carder PJ
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- Aged, Biopsy, Needle instrumentation, Biopsy, Needle methods, Breast pathology, Breast Diseases diagnosis, Breast Diseases diagnostic imaging, Breast Diseases pathology, Breast Neoplasms diagnosis, Diagnosis, Differential, Early Detection of Cancer methods, Female, Humans, Mammography, Middle Aged, Patient Selection, Vacuum, Breast Diseases surgery
- Abstract
Aims: Traditionally, a core biopsy diagnosis of radial scar will prompt diagnostic surgery because of the risk of associated malignancy. However, in the absence of atypia, the risk of malignancy is low. The recent introduction of the mammotome device facilitates vacuum-assisted large-volume sampling of a lesion, such that a benign diagnosis may be accepted more confidently, and if the lesion has been entirely removed, it effectively becomes a therapeutic procedure. The aim of this study was to review the role of mammotome excision in the management of non-atypical radial scars in the screening population., Methods: Screen-detected radial scars diagnosed on core biopsy between July 2004 and September 2008 were identified from pathology records. From January 2006, the mammotome device was used to excise non-atypical radial scars on core biopsy, as an alternative to surgery., Results: 22 core biopsy samples containing radial scars without atypia were included in the study; 14 were planned for mammotome excision and eight for diagnostic surgical excision. In the mammotome group, 78% (11/14) of patients had confirmation of non-atypical radial scars and thus avoided an operation. Three of the 14 cases planned for mammotome excision required surgery; in one case, the mammotome cores contained lobular in situ neoplasia, and, in two cases, attempts to sample the lesion with the mammotome were unsuccessful. Only one of the 22 cases ultimately proved malignant. This was a case of ductal carcinoma in situ arising within a radial scar, where the patient proceeded straight to surgery in view of discordance between radiological and pathological features., Conclusion: Utilisation of mammotome excision in the management of non-atypical radial scars successfully avoided surgery in 78% of eligible patients. Pathologists have an important role in selecting patients for mammotome excision by excluding the presence of atypia.
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- 2011
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10. Screen-detected pleomorphic lobular carcinoma in situ (PLCIS): risk of concurrent invasive malignancy following a core biopsy diagnosis.
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Carder PJ, Shaaban A, Alizadeh Y, Kumarasuwamy V, Liston JC, and Sharma N
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- Aged, Biopsy, Needle, Breast Neoplasms diagnostic imaging, Breast Neoplasms surgery, Carcinoma in Situ diagnostic imaging, Carcinoma in Situ surgery, Carcinoma, Lobular diagnostic imaging, Carcinoma, Lobular surgery, Female, Humans, Middle Aged, Radiography, Receptors, Estrogen metabolism, Breast Neoplasms pathology, Carcinoma in Situ pathology, Carcinoma, Lobular pathology
- Abstract
Aims: Pleomorphic lobular carcinoma in situ (PLCIS) is an uncommon, recently recognized variant of lobular carcinoma in situ (LCIS). Its natural history, biological behaviour and clinical characteristics are uncertain. The aim was to review the radiological and pathological findings in a series of screen-detected PLCIS diagnosed on needle core biopsy with a view to determining the diagnostic features, immunohistological profile and risk of concurrent invasive malignancy., Methods and Results: Ten cases of core biopsy-diagnosed, screen-detected PLCIS were identified. Core biopsy findings were compared with pathological findings at subsequent surgery. Two cases were associated with possible microinvasion on the core. Two of 10 had invasive lobular carcinoma and one had microinvasive lobular carcinoma on subsequent surgical excision (positive predictive value for malignancy = 30%). There was associated conventional LCIS on either core or excision biopsy in all cases except one. All three cases of oestrogen receptor (ER)-negative PLCIS arose in the context of ER+ conventional LCIS., Conclusions: PLCIS is a potentially more aggressive lesion than conventional LCIS and may present as mammographic calcification through a breast screening programme. Diagnosis may be problematic and immunohistochemical markers including ER may prove a useful diagnostic adjunct. There is a significant risk of concurrent invasive carcinoma following a core biopsy diagnosis., (© 2010 Blackwell Publishing Limited.)
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- 2010
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11. Large volume "mammotome" biopsy may reduce the need for diagnostic surgery in papillary lesions of the breast.
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Carder PJ, Khan T, Burrows P, and Sharma N
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- Biopsy methods, Breast Neoplasms diagnostic imaging, Calcinosis diagnostic imaging, Carcinoma, Papillary diagnostic imaging, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Mammography, Papilloma pathology, Ultrasonography, Mammary, Breast pathology, Breast Neoplasms pathology, Carcinoma, Papillary pathology
- Abstract
Background: There is currently debate as to whether all papillary lesions diagnosed on breast needle core biopsy (BNCB) require surgical excision. The development of large volume "mammotome" biopsy now permits non-operative removal. Few studies have assessed the usefulness of this approach., Aim: To review the pathological and radiological findings in a series of B3 and B4 papillary lesions identified on conventional BNCB with a view to assessing the usefulness of mammotome biopsy as a means of avoiding diagnostic surgery., Methods: All BNCBs from 23 June 2005 to 14 August 2007 that contained a B3 or B4 papillary lesion were identified by searching the pathology department records. Follow-up histology and radiological details were obtained., Results: 34 papillary BNCBs were included in this study: 21 from screen-detected lesions and 13 from patients presenting symptomatically. 31 were classified B3 and three were B4. Four cases included an atypical ductal epithelial proliferation (three B4, one B3). 14 patients had undergone open surgical biopsy, 15 had undergone mammotome excision, and five had had no subsequent procedure. All cases that had undergone mammotome biopsy had not shown atypia on the core, and 13 (87%) proved benign. In two cases the mammotome biopsy was either atypical or malignant, prompting surgery; the biopsy changes deriving from areas of ductal carcinoma in situ arising in the context of multiple intraduct papillomas and both were distinctive mammographically in presenting with large areas of segmental calcification. 11/14 cases that had undergone surgical excision had not shown atypia on the core, and proved benign. All three cases with atypia on the core proved malignant., Conclusion: In selected cases, mammotome biopsy may improve sampling of papillary lesions such that malignancy may be excluded without recourse to diagnostic surgery. Mammotome in such cases effectively acts as a therapeutic procedure. This has important implications for symptomatic and breast screening services.
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- 2008
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12. Examination of breast needle core biopsy specimens performed for screen-detected microcalcification.
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Kumaraswamy V and Carder PJ
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- Aged, Biopsy, Needle methods, Breast Diseases diagnostic imaging, Breast Diseases pathology, Breast Neoplasms diagnostic imaging, Calcinosis diagnostic imaging, Carcinoma, Ductal, Breast pathology, Diagnosis, Differential, Female, Humans, Mammography, Mass Screening, Middle Aged, Retrospective Studies, Breast pathology, Breast Neoplasms pathology, Calcinosis pathology
- Abstract
Aims: To establish the number of histological levels necessary for the evaluation of breast needle core biopsy (NCB) specimens taken from areas of mammographic calcification in patients presenting via the UK National Health Service Breast Screening Programme., Methods: Retrospective review of a series of breast NCB specimens initially examined routinely at nine levels. The presence of calcification within the histological sections in each of three sets of levels (levels 1-3, 4-6 and 7-9) and the (cumulative) diagnostic B category that would have pertained after each were assessed., Results: Accurate diagnostic classification was possible after examination of three levels in 89% cases. Examination of a further three levels permitted accurate diagnosis in a further eight cases (total 97% cases). In only three cases were nine levels necessary for accurate classification. In only a single case (1%) was it likely that routine examination of six levels could have led to significant misclassification. In a significant group of patients (18%), nine levels were considered to provide additional useful information, although this information did not alter the diagnosis., Conclusions: NCBs for screen-detected mammographic calcification should be routinely examined at six levels. Further levels may be needed in occasional cases to identify more conclusively the associated pathological abnormality. Further levels may be of particular value when assessing atypical intraductal proliferative epithelial lesions.
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- 2007
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13. Steroid hormone receptor expression in male breast cancer.
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Murphy CE, Carder PJ, Lansdown MR, and Speirs V
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- Breast Neoplasms, Male pathology, Humans, Immunohistochemistry, In Vitro Techniques, Male, Neoplasm Staging, Biomarkers, Tumor metabolism, Breast Neoplasms, Male metabolism, Estrogen Receptor alpha metabolism, Estrogen Receptor beta metabolism, Receptors, Androgen metabolism, Receptors, Progesterone metabolism
- Abstract
Aims: To investigate expression of the steroid hormone receptors estrogen receptor (ER)-alpha and -beta, progesterone receptor (PR) and androgen receptor (AR) in male breast cancer., Methods: Specimens from 16 male breast cancers were immunostained for ERalpha, ERbeta, PR and AR., Findings: Eighty-seven percent of tumours expressed ERalpha, 93% PR, 87% ERbeta and 87% AR. Staining for ERalpha and PR was confined exclusively to the nuclei of epithelial cells with some heterogeneity. Nuclear immunoreactivity was also observed with AR. Again this was restricted to epithelial cells but tended to be more uniform. ERbeta was seen in the nuclei of epithelial cells and also in stromal fibroblasts and lymphocytes. Analysis of serial sections revealed a similar pattern of staining with ERbeta and AR in epithelial cells., Conclusions: In addition to expression of the better known steroid receptors, ERalpha, PR and AR, we have demonstrated a high rate of expression of ERbeta in male breast cancer. This is in keeping with the generally high steroid receptor expression seen in males. However, the abundance of ERbeta expressed in this small series of male breast cancer is in contrast to female breast cancer where ERbeta expression is often reduced.
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- 2006
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14. Measurement of whole tumour size in breast cancer specimens.
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Littleford S and Carder PJ
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- Breast Neoplasms surgery, Carcinoma, Intraductal, Noninfiltrating surgery, Female, Humans, Mastectomy methods, Pathology, Surgical methods, Breast Neoplasms pathology, Carcinoma, Intraductal, Noninfiltrating pathology
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- 2005
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15. A multi-centre investigation towards reaching a consensus on the immunohistochemical detection of ERbeta in archival formalin-fixed paraffin embedded human breast tissue.
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Carder PJ, Murphy CE, Dervan P, Kennedy M, McCann A, Saunders PT, Shaaban AM, Foster CS, Witton CJ, Bartlett JM, Walker RA, and Speirs V
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- Female, Histocytological Preparation Techniques standards, Humans, Immunohistochemistry standards, Interinstitutional Relations, Ireland, Laboratories standards, Pilot Projects, Reference Standards, United Kingdom, Breast Neoplasms pathology, Estrogen Receptor beta isolation & purification, Histocytological Preparation Techniques methods, Immunohistochemistry methods
- Abstract
Estrogen receptor (ER) alpha is a well-established independent prognostic factor in breast cancer whose presence determines the clinical implications of adjuvant endocrine therapy. A second receptor, ERb has been described, and a number of studies have examined its expression in breast tissue. However elucidation of the role played by ERb has been hampered by published immunohistochemical studies employing a variety of protocols and scoring systems such that inter-laboratory comparisons are difficult. Here we present a multi-centre study designed to critically evaluate inter-laboratory differences in methodology. Six UK and Irish centres participated in this study. A small series of breast cancers were stained using centre-specific laboratory protocols and scored using both centrespecific and standard scoring protocols. There was generally poor agreement as to what constituted a positive or negative case when centre-specific scoring systems were used with less than half of all cases in agreement. Concordance was improved when a standard scoring system was used but varied according to threshold for positivity employed and primary antibody. Our results emphasise the need for further studies addressing the role of ERb to be based on a wider consensus on criteria for positivity. Ideally this should be based on calibration against clinical outcome.
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- 2005
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16. Atypical ductal hyperplasia in male breast tissue with gynaecomastia.
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Hamady ZZ, Carder PJ, and Brennan TG
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- Adult, Humans, Hyperplasia, Male, Breast pathology, Gynecomastia pathology
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- 2005
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17. Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast.
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Carder PJ, Garvican J, Haigh I, and Liston JC
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- Aged, Aged, 80 and over, Biopsy, Needle methods, Breast pathology, Carcinoma, Ductal, Breast pathology, Carcinoma, Intraductal, Noninfiltrating pathology, Diagnosis, Differential, Female, Humans, Hyperplasia pathology, Middle Aged, Reproducibility of Results, Biopsy, Needle standards, Breast Neoplasms pathology, Carcinoma, Papillary pathology, Papilloma pathology
- Abstract
Aims: To review 21 screen-detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non-malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain., Methods and Results: Forty-seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis' or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either 'B2', benign, 'B3', of uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19 'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All excised cases with a previous 'B3' or 'B2' were found benign, although four of the 'B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size., Conclusion: Our results confirm the accuracy of NCB in the diagnosis of screen-detected papillary lesions of the breast. Surgical excision may not always be necessary following a 'B3' core biopsy.
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- 2005
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18. Expression of prostate specific antigen in male breast cancer.
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Carder PJ, Speirs V, Ramsdale J, and Lansdown MR
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- Aged, Diagnosis, Differential, Humans, Infant, Male, Middle Aged, Breast Neoplasms, Male secondary, Prostate-Specific Antigen metabolism, Prostatic Neoplasms diagnosis
- Abstract
Male breast cancer is uncommon, accounting for less than 1% of all breast cancers. Carcinoma metastatic to the male breast is also unusual, with metastatic prostatic carcinoma being among the most common primary sites from which such tumours derive. Metastatic prostatic cancer and primary breast cancer may be histologically indistinguishable without immunohistochemistry because both often infiltrate with a cribriform architecture. Distinguishing between primary and metastatic disease within the breast is important because the treatment options for each are radically different. Following a case in which metastatic prostatic disease was initially wrongly diagnosed as primary breast cancer, a small series of male breast cancers was examined for expression of prostate specific antigen (PSA) and prostatic acid phosphatase to assess the usefulness of these markers in making this distinction. Focal expression of PSA was found in one of 11 cases of male breast cancer. These results indicate that PSA should be used with caution in this context.
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- 2005
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19. Fine needle aspiration cytology of the breast--time for a re-think?
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Carder PJ
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- Biopsy, Fine-Needle standards, Biopsy, Needle, Breast Neoplasms pathology, Cytodiagnosis methods, Cytodiagnosis standards, False Negative Reactions, False Positive Reactions, Female, Humans, Observer Variation, Breast Neoplasms diagnosis, Diagnostic Errors
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- 2004
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20. Could immunohistochemistry for p53 help tailor surgical treatment in endometrial carcinoma?
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Heatley MK and Carder PJ
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- Female, Humans, Immunohistochemistry, Biomarkers, Tumor analysis, Endometrial Neoplasms metabolism, Endometrial Neoplasms surgery, Tumor Suppressor Protein p53 metabolism
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- 2004
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21. Surgical excision is warranted following a core biopsy diagnosis of mucocoele-like lesion of the breast.
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Carder PJ, Murphy CE, and Liston JC
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- Adenocarcinoma, Mucinous metabolism, Adenocarcinoma, Mucinous surgery, Aged, Breast Neoplasms metabolism, Breast Neoplasms surgery, Carcinoma in Situ metabolism, Carcinoma in Situ surgery, Carcinoma, Ductal, Breast metabolism, Carcinoma, Ductal, Breast surgery, Female, Humans, Mass Screening, Middle Aged, Mucins metabolism, Adenocarcinoma, Mucinous pathology, Biopsy, Needle, Breast Neoplasms pathology, Carcinoma in Situ pathology, Carcinoma, Ductal, Breast pathology, Mucocele pathology
- Abstract
Aims: Mucocoele-like lesions (MLLs) of the breast are unusual lesions in which mucin-filled ducts or cysts are accompanied by extrusion of mucin into surrounding stroma. A possible diagnosis of MLL may be suggested by the finding of mucin-filled ducts or cysts and/or stromal mucin in a core biopsy sample. Whether such findings should prompt immediate open diagnostic biopsy to exclude malignancy is currently uncertain, although this represents current practice in our institution. In this study we have reviewed 11 cases of possible MLL on core biopsy correlating both pathological and radiological findings in order to determine the risks of associated malignancy and whether excision is the most appropriate management option., Methods and Results: Eleven cases of possible MLL presenting via the Breast Screening and Assessment Unit in Leeds since April 1999 were identified by review of pathological records. Histological slides, mammograms and ultrasound images were reviewed. Ten of the 11 had undergone open surgical biopsy for diagnosis. Three of the 10 (30%) proved to derive from malignant lesions. Two were ductal carcinoma in situ (DCIS) and one was an invasive mucinous carcinoma. All three cases had an associated atypical epithelial proliferation which, in a surgical excision, would be classified as atypical ductal hyperplasia (ADH) at least, as well as mucin in the core biopsy sample. The majority of possible MLLs presented radiologically as coarse calcification, but two of four (50%) which had a radiological mass subsequently proved malignant. Seven cases were without atypia on the core and all subsequently proved benign. Three of these, however, were associated with ADH on the excision biopsy., Conclusion: Surgical excision is warranted following a core biopsy suggestion of possible MLL when mucin-filled ducts or cysts and stromal mucin have been seen. The risk of malignancy is high when the core biopsy also contains an atypical epithelial proliferation (100% in our series) and also when there is an associated radiological mass lesion. In cases without atypia on the core a significant proportion of cases (43%) are associated with ADH on excision.
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- 2004
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22. Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model.
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Skliris GP, Munot K, Bell SM, Carder PJ, Lane S, Horgan K, Lansdown MR, Parkes AT, Hanby AM, Markham AF, and Speirs V
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- Age Factors, Azacitidine pharmacology, Breast Neoplasms genetics, Carcinoma, Ductal, Breast genetics, Carcinoma, Lobular chemistry, Carcinoma, Lobular genetics, Chi-Square Distribution, DNA Methylation drug effects, DNA Modification Methylases antagonists & inhibitors, Decitabine, Estrogen Receptor beta, Female, Humans, Immunohistochemistry methods, Lymphatic Metastasis, Neoplasm Recurrence, Local genetics, Receptors, Estrogen genetics, Reverse Transcriptase Polymerase Chain Reaction, Uterine Cervical Dysplasia chemistry, Uterine Cervical Dysplasia genetics, Azacitidine analogs & derivatives, Breast Neoplasms chemistry, Carcinoma, Ductal, Breast chemistry, Gene Silencing drug effects, Neoplasm Recurrence, Local chemistry, Receptors, Estrogen analysis, Tumor Cells, Cultured chemistry
- Abstract
To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation., (Copyright 2003 John Wiley & Sons, Ltd.)
- Published
- 2003
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23. Correspondence re: K. Heer et al., serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin. Cancer Res., 7: 3491-3494, 2001.
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Murphy CE, Lansdown MR, Speirs V, and Carder PJ
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- Carcinoma, Intraductal, Noninfiltrating blood, Cohort Studies, Humans, Plasma metabolism, Prognosis, Serum metabolism, Breast Neoplasms blood, Receptors, Estrogen blood, Vascular Endothelial Growth Factor A blood
- Published
- 2003
24. Utility of immunohistochemistry for CD99 in the identification of matrix-producing carcinoma of the breast.
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Walker JA and Carder PJ
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- 12E7 Antigen, Adult, Antigens, CD analysis, Biomarkers, Tumor metabolism, Breast Neoplasms chemistry, Breast Neoplasms pathology, Carcinoma, Intraductal, Noninfiltrating chemistry, Carcinoma, Intraductal, Noninfiltrating secondary, Cell Adhesion Molecules analysis, Female, Humans, Immunohistochemistry, Spinal Neoplasms chemistry, Spinal Neoplasms metabolism, Spinal Neoplasms secondary, Antigens, CD metabolism, Breast Neoplasms metabolism, Carcinoma, Intraductal, Noninfiltrating metabolism, Cell Adhesion Molecules metabolism, Extracellular Matrix metabolism
- Published
- 2003
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25. Will the spectrum of lesions prompting a "B3" breast core biopsy increase the benign biopsy rate?
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Carder PJ and Liston JC
- Subjects
- Biopsy, Biopsy, Needle, Breast Diseases pathology, Breast Neoplasms diagnostic imaging, Diagnosis, Differential, False Positive Reactions, Female, Humans, Mammography, Medical Audit, Middle Aged, Referral and Consultation, Breast pathology, Breast Neoplasms pathology, Mass Screening
- Abstract
Aim: To audit the benign surgical biopsies in women screened, assessed, and referred by the Leeds/Wakefield Breast Screening Unit for the year 1999-2000 with a view to determining any association with a preoperative B3 core biopsy categorisation., Methods: The results of all preoperative diagnostic procedures in all patients who underwent surgical excision for a lesion proving benign in the year 1999-2000 were reviewed. Cases were categorised according to whether the preoperative fine needle aspirate cytology (FNAC) or core biopsy had been equivocal or of uncertain malignant potential (C3/B3), inadequate or unrepresentative (C1/B1), or benign (C2/B2). In those cases with a C3/B3 FNAC or core biopsy result, reasons for the uncertainty were determined by examination of the report and, where necessary, slides. In cases with C1/B1 or C2/B2 investigations and in those without a preoperative procedure, the reasons for surgical referral were determined from the screening records. Case records of all patients with a B3 core biopsy categorisation who subsequently proved to have malignancy were also reviewed., Results: Thirty six women had benign surgical biopsies in the 1999-2000 screening year. In 13 of the 36 patients, referral for diagnostic biopsy rested on radiological and/or pathological suspicion of radial scar. The core biopsy category was B3 in all but one, which was in the B1 category. In a further 10 patients, referral was based primarily on a pathological B3 categorisation. The reasons for this were as follows: papillary lesion (two), fibroepithelial lesion (two), atypical intraductal epithelial proliferation (two), stromal mucin (two), atypical lobular hyperplasia (one), and an unusual vascular lesion (one). Two cases with a C3 on FNAC also derived from papillary lesions. In the remaining nine patients, the radiological features were sufficiently suspicious to prompt referral in the presence of either inadequate/unrepresentative (C1/B1) or benign (B2) preoperative pathological findings. Two women had no preoperative needle biopsy., Conclusions: In 22 of 36 benign biopsies, the initial core biopsy categorisation was B3. According to the current system of core biopsy categorisation, a diversity of lesions must be designated as of "uncertain malignant potential" (B3) because the technique provides insufficient tissue for full histological assessment. The use of this category may increase the number of benign biopsies if all such cases are referred for surgery. An increase in the benign biopsy rate may be averted if larger amounts of tissue can be obtained using newer vacuum assisted techniques such as the Mammotome.
- Published
- 2003
- Full Text
- View/download PDF
26. Oestrogen receptor beta: how should we measure this?
- Author
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Speirs V, Carder PJ, and Lansdown MR
- Subjects
- Antineoplastic Agents, Breast Neoplasms pathology, Cohort Studies, Estrogen Receptor beta, Female, Humans, Immunoenzyme Techniques, Biomarkers, Tumor metabolism, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Receptors, Estrogen metabolism
- Published
- 2002
- Full Text
- View/download PDF
27. Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue.
- Author
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Skliris GP, Parkes AT, Limer JL, Burdall SE, Carder PJ, and Speirs V
- Subjects
- Antibodies, Monoclonal immunology, Antibody Specificity, Biomarkers, Tumor analysis, Blotting, Western methods, Cryopreservation, Estrogen Receptor beta, Female, Flow Cytometry, Humans, Immunoenzyme Techniques, Neoplasm Proteins analysis, Neoplasm Proteins immunology, Paraffin Embedding, Receptors, Estrogen analysis, Biomarkers, Tumor immunology, Breast Neoplasms chemistry, Receptors, Estrogen immunology
- Abstract
Two oestrogen receptors, ER alpha and ER beta, exist. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. The aim of this study was to determine the utility of seven ER beta antibodies (14C8, 8D5, PAI313, PPG5/10, N19, 9.88, and D7N) raised against different domains of ER beta in three commonly used laboratory applications, namely immunohistochemistry, western blot, and flow cytometry, using human breast material. For immunohistochemical analysis of frozen material, PAI313 and D7N gave stronger and more specific signals than 14C8, 8D5, and PPG5/10. In paraffin sections, 14C8, closely followed by PPG5/10, gave by far the most superior nuclear immunoreactivity, compared with the other antibodies tested. In general, flow cytometry results mirrored the immunohistochemistry data for paraffin sections, with antibodies ranked 14C8 > 8D5> or = PAI-313 > PPG5/10 >D7N. For western blotting, 8D5 and D7N yielded the strongest and most consistent bands, with weaker bands seen with the others. It is concluded that ER beta protein can be detected using specific antibodies. However, there is considerable variation between the specificity and application of these antibodies, highlighting the fact that careful optimization is required when selecting an antibody for use in a particular laboratory technique., (Copyright 2002 John Wiley & Sons, Ltd.)
- Published
- 2002
- Full Text
- View/download PDF
28. Distinct expression patterns of ER alpha and ER beta in normal human mammary gland.
- Author
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Speirs V, Skliris GP, Burdall SE, and Carder PJ
- Subjects
- Estrogen Receptor alpha, Estrogen Receptor beta, Female, Humans, Immunohistochemistry methods, Reverse Transcriptase Polymerase Chain Reaction, Breast metabolism, Receptors, Estrogen metabolism
- Abstract
Aim: Two oestrogen receptors (ERs) have been identified to date-the "classic" ER alpha and the more recently described ER beta. Although much is known about ER alpha at the mRNA and protein levels, our knowledge of the expression and distribution of ER beta protein is much more limited. The aim of this study was to compare the cellular distribution of ER alpha and ER beta in normal human mammary gland., Methods: Formalin fixed, paraffin wax embedded material was obtained from reduction mammoplasty specimens, normal tissue adjacent to breast tumour, or fibroadenoma. Sections were immunohistochemically stained for ER alpha, ER beta, and the progesterone receptor. The staining pattern for each antibody was evaluated and compared., Results: ER alpha was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ER beta was also seen in these cells, additional strong staining was detected specifically in the cell nuclei of myoepithelial cells. Occasional staining was seen in surrounding stromal and endothelial cell nuclei and in lymphocytes., Conclusions: ER subtypes have distinct distribution patterns in the normal mammary gland. The widespread distribution of ER beta suggests that it may be the dominant ER in the mammary gland where it may be acting as a natural suppressor.
- Published
- 2002
- Full Text
- View/download PDF
29. How would you classify this fine needle aspirate of breast: C2-5?
- Author
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Stahlschmidt J, Liston J, Aslam MM, and Carder PJ
- Subjects
- Adenocarcinoma pathology, Aged, Breast Neoplasms diagnostic imaging, Breast Neoplasms pathology, Diagnosis, Differential, Female, Humans, Hyalin metabolism, Immunohistochemistry, Prognosis, Radiography, Staining and Labeling, Adenocarcinoma diagnosis, Biopsy, Needle methods, Breast Neoplasms diagnosis
- Published
- 2001
30. New mammographic stromal deformity: what is the significance of this finding on screening mammograms?
- Author
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Haigh LI, Liston JC, and Carder PJ
- Abstract
Current practice within the NHS Breast Screening Programme recommends surgical excision of screen detected areas of stromal deformity as differentiating carcinomas from radial scars and excluding in situ malignancy in association with radial scars is unreliable. We retrospectively reviewed all cases recalled for assessment over a 4 year period, identified to have an area of persistent stromal deformity not associated with surgical scarring and without an associated mammographic mass. Thirty women were prevalent (first) round screens--17 cases proved to be malignant and 13 benign. The latter group included three cases of atypical ductal hyperplasia. Nineteen women were incident (subsequent) round screens--all 19 cases proved to be malignant. This study supports the practice of surgically removing all areas of stromal deformity, particularly new areas of stromal deformity detected in the incident round, as in this group the likelihood of malignancy is extremely high.
- Published
- 2001
- Full Text
- View/download PDF
31. Educational case report. Fine needle aspiration cytology of adenoid cystic carcinoma of the breast.
- Author
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Stahlschmidt J, Liston J, Aslam MM, and Carder PJ
- Subjects
- Aged, Breast Neoplasms diagnostic imaging, Diagnosis, Differential, Female, Humans, Hyalin metabolism, Immunohistochemistry, Mammography, Staining and Labeling methods, Ultrasonography, Mammary, Biopsy, Needle methods, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Carcinoma, Adenoid Cystic diagnosis, Carcinoma, Adenoid Cystic pathology, Cytodiagnosis
- Published
- 2001
- Full Text
- View/download PDF
32. Immunohistochemical detection of ERbeta in breast cancer: towards more detailed receptor profiling?
- Author
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Skliris GP, Carder PJ, Lansdown MR, and Speirs V
- Subjects
- Breast chemistry, Breast pathology, Breast Neoplasms pathology, Estrogen Receptor alpha, Estrogen Receptor beta, Female, Humans, Immunohistochemistry, Breast Neoplasms metabolism, Receptors, Estrogen analysis
- Abstract
Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERbeta has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemical detection of ERbeta in archival breast tumours., (Copyright 2001 Cancer Research Campaign.)
- Published
- 2001
- Full Text
- View/download PDF
33. Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen.
- Author
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Adams J, Carder PJ, Downey S, Forbes MA, MacLennan K, Allgar V, Kaufman S, Hallam S, Bicknell R, Walker JJ, Cairnduff F, Selby PJ, Perren TJ, Lansdown M, and Banks RE
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Platelets metabolism, Disease Progression, Endothelial Growth Factors blood, Female, Humans, Immunohistochemistry, Lymphokines blood, Middle Aged, Neoplasm Metastasis, Remission Induction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Antineoplastic Agents, Hormonal pharmacology, Breast Neoplasms blood, Breast Neoplasms blood supply, Breast Neoplasms metabolism, Endothelial Growth Factors biosynthesis, Lymphokines biosynthesis, Microcirculation metabolism, Tamoxifen pharmacology
- Abstract
The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.
- Published
- 2000
34. Ovarian haemangiomas and stromal luteinization.
- Author
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Carder PJ and Gouldesbrough DR
- Subjects
- Adenocarcinoma pathology, Female, Humans, Middle Aged, Stromal Cells pathology, Endometrial Neoplasms pathology, Hemangioma pathology, Luteal Cells pathology, Neoplasms, Multiple Primary pathology, Ovarian Neoplasms pathology
- Published
- 1995
- Full Text
- View/download PDF
35. A study of stabilisation of p53 protein versus point mutation in colorectal carcinoma.
- Author
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Cripps KJ, Purdie CA, Carder PJ, White S, Komine K, Bird CC, and Wyllie AH
- Subjects
- Base Sequence, Humans, Immunohistochemistry, Molecular Sequence Data, Polymerase Chain Reaction, Colorectal Neoplasms genetics, Point Mutation, Tumor Suppressor Protein p53 analysis
- Abstract
Abnormalities of the p53 tumour suppressor gene occur in many types of cancer including approximately 60% of colorectal carcinomas. This study investigates in 47 colorectal carcinomas the relationship between stabilised p53 protein detected by immunocytochemistry (ICC), and p53 mutation. 27 cases stained positively with the antibody PAb1801. Sequencing of exons 5-8 revealed 19 mutations in 18 of these cases (one tumour contained two different mutations). A rapid, non-radioactive method was developed to screen for mutations in this region of the gene involving Single Strand Conformational Polymorphism analysis (SSCP) and a MspI restriction digestion. This screen detected 17/19 (89%) of the sequenced mutations, and a further four mutations in 20 PAb1801 negative cases that were confirmed by sequencing. Reproducibility of ICC in detecting stabilised protein was assessed by restaining the 47 cases with the antibody DO7 after pre-treatment to optimise detection. Fewer cases were negative with DO7 although overall concordance with PAb1801 was good. A substantial proportion of carcinomas with stabilised p53 as detected by ICC do not contain mutations in exons 5-8, whilst some mutations (the majority in exon 6) are not associated with stabilisation.
- Published
- 1994
36. Apoptosis in carcinogenesis: the role of p53.
- Author
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Wyllie AH, Carder PJ, Clarke AR, Cripps KJ, Gledhill S, Greaves MF, Griffiths S, Harrison DJ, Hooper ML, and Morris RG
- Subjects
- Aneuploidy, Cell Survival genetics, Cell Survival radiation effects, Colorectal Neoplasms genetics, G1 Phase genetics, Gene Rearrangement, Humans, Models, Biological, Mutation, Neoplasms etiology, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Apoptosis genetics, Genes, p53, Neoplasms genetics
- Published
- 1994
- Full Text
- View/download PDF
37. Multiple lymphomatous polyposis and the role of fine needle aspiration cytology.
- Author
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Carder PJ and Gouldesbrough DR
- Subjects
- Aged, Biopsy, Needle, Diagnosis, Differential, Humans, Intestinal Mucosa pathology, Kidney pathology, Liver pathology, Male, Gastrointestinal Neoplasms pathology, Lymphoma, B-Cell pathology, Polyps pathology
- Abstract
Multiple lymphomatous polyposis is an uncommon but distinctive form of gastrointestinal lymphoma. Clinical symptoms may closely resemble those of colorectal carcinoma and diagnostic confusion may result. The condition has a characteristic pathological appearance and immunophenotype which is important in allowing distinction from other less aggressive forms of gastrointestinal lymphoma. We report a case of this unusual condition in which the diagnosis was aided by fine needle aspiration cytology.
- Published
- 1993
- Full Text
- View/download PDF
38. Atrial myxoma: tumour or trauma?
- Author
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Nolan J, Carder PJ, and Bloomfield P
- Subjects
- Aged, Echocardiography, Heart Neoplasms diagnostic imaging, Heart Neoplasms pathology, Heart Septum injuries, Humans, Male, Myxoma diagnostic imaging, Myxoma pathology, Heart Injuries complications, Heart Neoplasms etiology, Myxoma etiology
- Abstract
A mass lesion developed in the right atrium at the site of a trans-septal puncture after percutaneous balloon dilatation of the mitral valve in a man aged 74. The lesion had the pathological appearance of an atrial myxoma and seemed to have developed after trauma to the intra-atrial septum. This case suggests that at least some atrial myxomas are reactive rather than neoplastic in origin.
- Published
- 1992
- Full Text
- View/download PDF
39. Distribution of glutathione S-transferase isoenzymes in human ovary.
- Author
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Rahilly M, Carder PJ, al Nafussi A, and Harrison DJ
- Subjects
- Corpus Luteum enzymology, Cytoplasm enzymology, Female, Humans, Immunoenzyme Techniques, Menstruation metabolism, Microsomes enzymology, Ovarian Follicle enzymology, Ovary metabolism, Pregnancy, Glutathione Transferase analysis, Gonadal Steroid Hormones metabolism, Isoenzymes analysis, Ovary enzymology
- Abstract
Glutathione S-transferases (GST) are drug-metabolizing and detoxification enzymes involved in the intracellular transport and metabolism of steroid hormones. We studied expression of pi, alpha, mu and microsomal GST by immunohistochemistry in normal human ovaries at different stages of the menstrual cycle and pregnancy and after the menopause. Antibodies were raised in rabbits to purified GST subunits and formalin-fixed, paraffin-embedded sections were studied using the peroxidase-antiperoxidase method. Staining density was graded from very strong to negative. All four isoenzymes were identified in the ovary and their distribution was heterogeneous. The staining pattern of follicles varied with the stage of the menstrual cycle for each isoenzyme. All the ovaries contained abundant GST pi in stroma. GST alpha is closely associated with the glutathione-dependent enzyme delta-5,3-ketosteroid isomerase, which catalyses the conversion of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione. GST alpha was localized to the steroid-producing cells and thus may be useful in studying ovaries in conditions where there are assumed alterations in steroid production.
- Published
- 1991
- Full Text
- View/download PDF
40. Glutathione S-transferase detoxication enzymes in cervical neoplasia.
- Author
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Carder PJ, al-Nafussi A, Rahilly M, Lauder J, and Harrison DJ
- Subjects
- Carcinoma, Squamous Cell enzymology, Cervix Uteri enzymology, Cervix Uteri pathology, Female, Humans, Immunohistochemistry, Isoenzymes metabolism, Microsomes enzymology, Uterine Cervical Neoplasms pathology, Biomarkers, Tumor analysis, Glutathione Transferase metabolism, Uterine Cervical Neoplasms enzymology
- Abstract
Altered expression of the glutathione S-transferases (GSTs) has been implicated in the progression to tumour after exposure to carcinogens, and GST Pi has been suggested as a possible marker of preneoplasia in the cervix. We have studied expression of the GST isoenzymes in normal cervix, non-dysplastic cervical condylomata, cervical intraepithelial neoplasia (CIN), and invasive squamous carcinoma of the cervix using immunocytochemistry. An increase in GST Pi in CIN as compared with normal cervix was paralleled by a reduction in the expression of microsomal GST. Similar changes were seen in cervical condylomata and immature squamous metaplasia, and thus neither isoenzyme is a marker of dysplasia. Microsomal GST was expressed in only 66 per cent of cases and in 22 per cent showed strong expression in vascular endothelium. These findings are of particular interest in view of the association between cervical carcinoma and cigarette smoking. Differences between individuals in the ability to detoxify environmental carcinogens may influence the likelihood of progression from benign proliferation to invasive malignancy.
- Published
- 1990
- Full Text
- View/download PDF
41. Glutathione S-transferase in human brain.
- Author
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Carder PJ, Hume R, Fryer AA, Strange RC, Lauder J, and Bell JE
- Subjects
- Adult, Aging metabolism, Cerebellum enzymology, Cerebral Cortex enzymology, Cerebral Ventricles enzymology, Choroid Plexus enzymology, Cytosol enzymology, Female, Gestational Age, Glutathione Transferase immunology, Humans, Immunoblotting, Immunohistochemistry, Isoenzymes metabolism, Pineal Gland enzymology, Pregnancy, Subarachnoid Space enzymology, Brain enzymology, Glutathione Transferase metabolism
- Abstract
The glutathione S-transferases are a complex group of multifunctional enzymes which may detoxify a wide range of toxic substances including drugs and carcinogens. Different isoenzymes vary in substrate specificity, tissue distribution and level of expression during development. Following reports of cell-specific and age-dependent expression in rat brain we have studied, immunohistochemically, expression of the Pi and Alpha class isoenzymes in 10 adult and 21 human fetal brains. Whilst Alpha isoenzyme is expressed only in adult brain, and then only focally, Pi isoenzyme is strongly expressed from as early as 12 weeks gestation. In the adult, expression is localized to choroid plexus, vascular endothelium, ventricular lining cells, pia-arachnoid and astrocytes. In fetal brain, expression is also strong in cells with the morphology of tanycytes and in the cell bodies of radial glia. Neurons are consistently negative. Pi isoenzyme thus localizes to the sites of the blood-CSF barrier, blood-brain barrier, CSF-brain barrier and pia-arachnoid-brain barrier. It is ideally placed to regulate neuronal exposure to potentially toxic substances derived from blood or cerebrospinal fluid. Expression so early in gestation is of significance and may imply a role in protection of the developing human brain.
- Published
- 1990
- Full Text
- View/download PDF
42. Heterotopic brain presenting as a cystic mass of the palate.
- Author
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al-Nafussi A, Hancock K, Sommerlad B, and Carder PJ
- Subjects
- Choroid Plexus pathology, Humans, Immunohistochemistry, Infant, Newborn, Male, Staining and Labeling, Brain, Choristoma pathology, Lymphangioma pathology, Palatal Neoplasms pathology
- Abstract
We report a case of heterotopic brain which presented as a cystic mass in the palate and which clinically was thought to be a cystic hygroma. Histologically, there was a remarkable proliferation of choroid plexus-like structures which we believe to have been responsible for the production of cerebrospinal fluid. We believe heterotopic brain to result from early displacement of multipotential cells and that the presence of cerebrospinal fluid within extracranial brain tissue does not imply an intracranial communication.
- Published
- 1990
- Full Text
- View/download PDF
43. Monoclonal antibodies in the cytodiagnosis of serous effusions.
- Author
-
al-Nafussi A and Carder PJ
- Subjects
- Antigens, Neoplasm analysis, Ascitic Fluid etiology, Carcinoembryonic Antigen analysis, Cytodiagnosis methods, Humans, Immunoenzyme Techniques, Keratins analysis, Membrane Glycoproteins analysis, Mucin-1, Pleural Effusion etiology, Pleural Effusion, Malignant diagnosis, Antibodies, Monoclonal, Ascitic Fluid cytology, Pleural Effusion pathology
- Abstract
In order to assess the value of immunocytochemical staining as a method of discriminating between benign reactive mesothelial cells and malignant epithelial cells in serous effusions, we have studied the reactions of a panel of commercially available antibodies on cells harvested from 83 pleural and peritoneal fluids and compared the results with the clinical and cytological diagnoses. The antibodies used were raised against cytokeratin (PKK1), epithelial membrane antigen (EMA), carcino-embryonic antigen (CEA), pregnancy specific B1-glycoprotein (SP1) and leucocyte common antigen (LCA). Anti-CEA was positive in 16 of 39 effusions (41%) containing carcinoma cells. Pregnancy specific B1-glycoprotein (SP1) was positive in 33% of the same samples. Mesothelial cells did not stain with these antibodies. Thus anti-CEA and SP1 can be used to discriminate between benign mesothelial and malignant epithelial cells in effusions. Anti-PKK1 stained both benign reactive mesothelial cells and malignant epithelial cells and cannot be used to discriminate between these two cell types. Strong positive staining of malignant cells was noted with anti-EMA. However, as occasional weak staining of mesothelial cells was also noted, strong staining with this antibody may be regarded as suspicious but not conclusive of malignancy.
- Published
- 1990
- Full Text
- View/download PDF
44. Rapidly progressive cardiac failure due to lymphomatous infiltration of the myocardium.
- Author
-
Gouldesbrough DR and Carder PJ
- Subjects
- Heart Neoplasms pathology, Heart Ventricles, Humans, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Myocardium pathology, Testicular Neoplasms pathology, Testis pathology, Heart Failure etiology, Heart Neoplasms complications, Lymphoma, Non-Hodgkin complications
- Abstract
A case of myocardial infiltration by lymphoma causing rapidly progressive cardiac failure is described. The clinical and pathological features are detailed and the rarity of this mode of presentation of cardiac involvement by lymphoma is emphasized.
- Published
- 1989
- Full Text
- View/download PDF
45. Opportunistic infection and antineutrophil cytoplasm antibodies in Wegener's granulomatosis.
- Author
-
Carder PJ and Harrison DJ
- Subjects
- Cytoplasm immunology, Female, Granulomatosis with Polyangiitis complications, Humans, Male, Middle Aged, Opportunistic Infections pathology, Autoantibodies analysis, Granulomatosis with Polyangiitis diagnosis, Neutrophils immunology, Opportunistic Infections complications
- Abstract
Antineutrophil cytoplasmic antibodies (ANCA) are of established value in the diagnosis of Wegener's granulomatosis allowing early introduction of therapy. These patients are at risk of opportunistic infection, especially whilst receiving immunosuppressive drugs and this may mimic reactivation of disease. We present three cases of Wegener's granulomatosis complicated by opportunistic infection and assess the value of ANCA detection. Two presented with symptoms compatible with disease reactivation but ANCA were negative. One died with pulmonary infection due to Pneumocystis carinii, Aspergillus fumigatus and Herpes simplex. Transbronchial biopsy in the second case revealed Pneumocystis carinii. A third case had strongly positive serum ANCA at diagnosis but in addition pulmonary infection with Legionella pneumophila. ANCA detection is of value in patients with Wegener's granulomatosis, but the result must be interpreted in the full clinical context.
- Published
- 1989
- Full Text
- View/download PDF
46. Teaching systemic pathology in Edinburgh.
- Author
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Gouldesbrough DR, Carder PJ, Piris J, and Bird CC
- Subjects
- Curriculum, Humans, Scotland, Education, Medical, Undergraduate, Pathology education
- Published
- 1988
- Full Text
- View/download PDF
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