C W Elston

University of Nottingham, Nottingham, ENG, United Kingdom

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Publications (272)1020.65 Total impact

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    ABSTRACT: Standard margin assessment of breast carcinoma surgical specimens uses radial sections perpendicular to the margin. Shave sections assess a larger surface area of margin than radial sections. The aim was to assess the value of additional shave sections of the margin. Both types of section were used to assess 471 wide local excision specimens for invasive carcinoma. One hundred and seventy-nine specimens had positive margins: only radial margins were involved (tumour within 5 mm of margin) in 76, only shave margins in 45, and both shave and radial margins in 58. Residual carcinoma was found in re-excision specimens (immediate or later) in 43% when the closest distance to the radial margin was 0-1 mm, 25% for 2-4 mm, 18% for 5-9 mm and 13% for >9 mm. Residual carcinoma was found in 44% of specimens if any shave section was positive and in 9% if all shaves were negative. Residual carcinoma was found in 32% if either radial or shave sections were positive and in 4% if neither was positive. The combination of radial and shave sections appears to be good at separating patients into two groups with high and low risk of residual carcinoma.
    Histopathology 04/2010; 56(5):573-80. · 2.86 Impact Factor
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    ABSTRACT: The new gene expression molecular taxonomy of breast cancer places medullary carcinoma in the basal group. The basal group is considered to have a poor prognosis, but medullary carcinoma is considered to have a better prognosis than other grade 3 carcinomas. The prognostic significance of tumour associated inflammation, an important feature of medullary carcinomas, remains controversial. The aim of this study was to assess the prognostic importance of medullary histological type and inflammation in breast cancer. One thousand five hundred and ninety-seven patients who received no systemic adjuvant treatment and who had a median follow up of 9.5 years were studied. Results: Prominent inflammation was associated with high histological grade and with better survival [relative risk (RR) 0.57, 95% confidence intervals (CI) 0.44-0.74] on multivariate analysis. Typical and atypical medullary carcinomas (n=132) did not have significantly different survival and were grouped together. Medullary carcinoma did not have significantly different prognosis than grade 3 ductal carcinoma with prominent inflammation, but both had a better prognosis than grade 3 ductal carcinoma without prominent inflammation (P<0.0001 and P=0.03). These differences were independent of other prognostic factors. These results question the current separation of typical and atypical medullary carcinoma. Prominent inflammation is associated with a better prognosis, and may explain the better prognosis in medullary carcinoma compared with grade 3 ductal carcinoma without prominent inflammation. The good prognosis of medullary carcinoma emphasises the heterogeneity of basal-like breast carcinomas. Further studies are needed to investigate the difference in survival between medullary carcinoma and other forms of basal carcinomas and the role of inflammation in any such differences in behaviour.
    European journal of cancer (Oxford, England: 1990) 04/2009; 45(10):1780-7. · 4.12 Impact Factor
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    ABSTRACT: The three strongest prognostic determinants in operable breast cancer used in routine clinical practice are lymph node (LN) stage, primary tumor size, and histologic grade. However, grade is not included in the recent revision of the TNM staging system of breast cancer as its value is questioned in certain settings. This study is based on a large and well-characterized consecutive series of operable breast cancer (2,219 cases), treated according to standard protocols in a single institution, with a long-term follow-up (median, 111 months) to assess the prognostic value of routine assessment of histologic grade using Nottingham histologic grading system. Histologic grade is strongly associated with both breast cancer-specific survival (BCSS) and disease-free survival (DFS) in the whole series as well as in different subgroups based on tumor size (pT1a, pT1b, pT1c, and pT2) and LN stages (pN0 and pN1 and pN2). Differences in survival were also noted between different individual grades (1, 2, and 3). Multivariate analyses showed that histologic grade is an independent predictor of both BCSS and DFS in operable breast cancer as a whole as well as in all studied subgroups. Histologic grade, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive breast cancer and should be incorporated in breast cancer staging systems.
    Journal of Clinical Oncology 08/2008; 26(19):3153-8. · 18.04 Impact Factor
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    ABSTRACT: The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological-pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological-pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2008; 452(5):473-9. · 2.68 Impact Factor
  • A H S Lee, Z Hodi, I O Ellis, C W Elston
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    ABSTRACT: To identify features useful in distinguishing phyllodes tumours from fibroadenomas on core biopsy. Starting from the diagnosis made on the surgical specimen, 12 features in the previous core biopsy specimens were analysed. Thirty-six phyllodes tumours had 44 previous core biopsy specimens, which were reported as fibroadenoma in 11 and spindle cell lesion of uncertain nature in one, and included phyllodes tumour in the differential diagnosis in 32. The lesions with a core diagnosis of fibroadenoma were excised largely because they were growing or exceeded 30 mm; review of the corresponding surgical specimen showed heterogeneous stromal cellularity. Thirty-eight fibroadenomas had previous core biopsy specimens reported as fibroadenoma in 37, and one of which included phyllodes tumour in the differential diagnosis. The following four features were significantly more common in cores from phyllodes tumours and had a kappa statistic of > 0.6 in a reproducibility study: stromal cellularity increased in at least 50% compared with typical fibroadenoma, stromal overgrowth (x10 field with no epithelium), fragmentation and adipose tissue within stroma. This study describes features useful in the diagnosis of phyllodes tumour on core biopsy. Some core biopsy specimens from phyllodes tumours show features of fibroadenoma on core biopsy because of tumour heterogeneity.
    Histopathology 09/2007; 51(3):336-44. · 2.86 Impact Factor
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    ABSTRACT: To obtain better survival estimates for the individual than is provided by placement in an NPI group. Consecutive primary operable breast cancers treated at Nottingham City Hospital 1990-1999. Ten year % actuarial survivals plotted for 10 ranges of NPI from 2.0 to 6.9. There is an excellent inverse correlation between median NPI value for each range and survival at 10 years. To enable estimation of survival for all individual values of NPI, a curve fitting technique applied to these results (by G.B.) gave the formula to estimate survival from the individual's NPI score: 10 year % survival for the individual=-3.0079 x NPI(2)+12.30 x NPI+83.84. This gave an r(2) of 0.98. Greater accuracy in individual survival prediction is obtained by dividing women into 10 groups by NPI scores than in the originally described six groups; rank order of survival in relation to NPI score is preserved. A curve fitting technique has been applied to these data to give a formula for the prediction of 10 year survival for every 0.1 value of NPI.
    European Journal of Cancer 08/2007; 43(10):1545-7. · 5.06 Impact Factor
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    ABSTRACT: The Nottingham Prognostic Index (NPI) is a well established and widely used method of predicting survival of operable primary breast cancer. Primary: To present the updated survival figures for each NPI Group. Secondary: From the observations to suggest reasons for the reported fall in mortality from breast cancer. The NPI is compiled from grade, size and lymph node status of the primary tumour. Consecutive cases diagnosed and treated at Nottingham City Hospital in 1980-1986 (n=892) and 1990-1999 (n=2,238) are compared. Changes in protocols towards earlier diagnosis and better case management were made in the late 1980s between the two data sets. Case survival (Breast Cancer Specific) at 10 years has improved overall from 55% to 77%. Within all Prognostic groups there are high relative and absolute risk reductions. The distribution of cases to Prognostic groups shows only a small increase in the numbers in better groups. The updated survival figures overall and for each Prognostic group for the NPI are presented.
    European Journal of Cancer 08/2007; 43(10):1548-55. · 5.06 Impact Factor
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    ABSTRACT: To assess the reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast. Previous studies have mostly been small, with a range of agreement from 62% to 100%. Retrospective audit of 338 tumours surgically excised within 60 days of core biopsy, that had had oestrogen receptor assessed on both the core biopsy and tumour specimens. Surgical specimens were incised when fresh to ensure good fixation. External controls including a weakly positive tumour were included in each immunohistochemistry run. Oestrogen receptor expression was bimodal, with H score in both specimens of either 0 or >50 in 96% of tumours. Using H score cut-off of 10 for positivity, there was an agreement between core and excision in 334 of 338 tumours (98.8%). All discrepancies were between weakly positive and negative tumours. Intratumoral heterogeneity could explain the one tumour that was negative on core and positive on excision. H score tended to be slightly higher on core than excision (means 146 and 136). Better fixation on the core is the most likely explanation for this and for the three tumours that were positive on core and negative on excision. Repeat staining on tumours with discrepant results gave similar results in all except one case. An internal control was present in 97% of excisions and 55% of cores of oestrogen receptor-negative tumours; the internal control stained positively in all except two sections. Oestrogen receptor can be assessed reliably on needle core biopsies of invasive carcinomas of the breast.
    Journal of Clinical Pathology 03/2007; 60(3):299-302. · 2.44 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2007; 5(3):27-27.
  • Ejc Supplements - EJC SUPPL. 01/2007; 5(3):19-19.
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    ABSTRACT: This study aimed to test the hypothesis that lymphovascular invasion adds prognostic information to histological grade and tumour size in node-negative invasive carcinoma of the breast. Lymphovascular invasion was assessed in haematoxylin and eosin tumour sections from 2760 patients with node-negative invasive breast carcinoma treated with definitive surgery. Patients were divided into two groups: 990 in the no adjuvant therapy series (diagnosed in 1974-1988) with median follow-up of 13 years; and 1765 in the selective adjuvant therapy series (1988-2000) with median follow-up of 6.8 years. Lymphovascular invasion was identified in 19% of tumours and was associated with larger tumour size, higher histological grade and younger age. Overall, survival was associated on multivariate analysis with lymphovascular invasion, histological grade and tumour size in both patient series, and with histological type in the no adjuvant therapy series. In conclusion, lymphovascular invasion is an independent prognostic factor in node-negative breast cancer and should be considered in decisions about adjuvant treatment in this group of women.
    European Journal of Cancer 03/2006; 42(3):357-62. · 5.06 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2006; 4(2):130-130.
  • Ejc Supplements - EJC SUPPL. 01/2006; 4(2):125-125.
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    ABSTRACT: Considerable progress has been made in understanding breast lesions utilizing molecular methods, but conventional morphology, simple immunohistochemical stains and common sense still prevail in diagnosing the vast majority of breast disease. The focus of this review is to identify the most common breast lesions sent to our consultation practice, and to reiterate salient diagnostic features, differential diagnoses and common pitfalls in identifying these lesions. Separation of epithelial proliferative lesions and differentiation between usual epithelial hyperplasia (UEH) and atypical ductal hyperplasia (ADH) are the most common problems encountered in our Consultation practice. Differentiation between UEH and ADH is based on the assumption that ADH is a clonal process, recognized by a uniform phenotype and more recently described immunohistochemical markers such as differential cytokeratin and also hormone receptor expression. Difficulty in subtyping invasive carcinomas and exclusion of in situ and/or invasive carcinoma in a sclerosing lesion is also commonly noted. Finally, problems in distinguishing various papillary and fibroepithelial lesions are also encountered. The use of common immunohistochemical stains such as various cytokeratin and myoepithelial markers, E-cadherin and hormone receptors is helpful in solving most of these diagnostic dilemmas.
    Histopathology 12/2005; 47(5):445-57. · 2.86 Impact Factor
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    ABSTRACT: To assess the value of nipple and quadrant sections in mastectomy specimens for carcinoma in detecting Paget's disease and multifocal carcinoma. Two hundred and forty eight consecutive mastectomies performed for carcinoma were reviewed. The presence of Paget's disease of the nipple and mode of identification of any multifocal carcinoma was recorded. Nipple sections showed Paget's disease in eight specimens: in five the diagnosis had been made on previous biopsy and in three (1%) this was a new diagnosis. In the 220 specimens in which all four quadrants were sampled, multifocal disease was identified more often in specimens with invasive carcinoma (39 of 186; 21%) than in those with only ductal carcinoma in situ (0 of 34). In specimens with invasive carcinoma, multifocality was identified macroscopically in 20: on microscopy of tumour sections in four, on microscopic examination of quadrant sections in 11, in the nipple in three, and in both quadrant and nipple sections in one. Overall, multifocality was found on microscopic examination of quadrant or nipple sections in 15 of 220 specimens (7%). The low frequency of detection of multifocality or Paget's disease in nipple and quadrant sections from mastectomy specimens, combined with the fact that such findings do not affect patient management, suggest that nipple and quadrant sections should only be taken if resources permit.
    Journal of Clinical Pathology 06/2005; 58(5):543-5. · 2.44 Impact Factor
  • C W Elston
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    ABSTRACT: The main reasons for applying a classification system to invasive breast carcinoma are to obtain a correlation with prognosis and tumour biology. Invasive carcinomas may be sub-divided morphologically according to their degree of differentiation. This is achieved in two ways, by assessing histological type and histological grade. A wide range of histological patterns is recognised in invasive carcinoma of the breast and four broad prognostic groups are recognised: the excellent prognosis group comprises tubular, cribriform, mucinous carcinomas; the good group tubular mixed, mixed ductal NST/special type and classical lobular carcinoma; the average group mixed lobular, medullary and atypical medullary carcinoma and the poor group is composed of ductal NST, mixed ductal and solid lobular carcinoma understanding of the biology of breast cancer. For example, tumours with a medullary phenotype which express basal cytokeratins and are p53 positive and ER and c-erbB-2 negative are strongly predictive of the BRCA-1 gene-mutation carrier state. Histological grading refers to the semi-quantitative evaluation of the morphological structure of breast carcinomas. In the Nottingham method three characteristics of the tumour are evaluated, glandular differentiation, nuclear pleomorphism and mitotic counts. A numerical scoring system on a scale of 1-3 is used to ensure that each factor is assessed individually. Overall grade is assigned as follows: Grade 1: 3-5 points, Grade 2: 6-7 points, Grade 3: 8-9 points. There is a highly significant relationship between histological grade and prognosis; survival worsens with increasing grade. Histological grading has been shown to have good reproducibility and has been adopted for use in Europe, Australasia and the United States. When combined with pathological tumour size and lymph node stage into the Nottingham Prognostic Index there is excellent stratification for patient management.
    Verhandlungen der Deutschen Gesellschaft für Pathologie 02/2005; 89:35-44.
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    ABSTRACT: To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2004; 445(2):119-28. · 2.68 Impact Factor
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    ABSTRACT: Bilateral breast cancers that develop at similar times in an individual are likely to have been subjected to similar hormonal, environmental and genetic influences during tumourogenesis compared with metachronous tumours. As such, it is possible that tumour phenotype in synchronous bilateral breast cancer may display similar biological characteristics. The aim of this study was to identify phenotypic similarities between synchronous and metachronous bilateral breast cancers which may suggest a common origin. Thirty-three cases of synchronous and 46 cases of metachronous bilateral breast cancer that displayed similar tumour type were analysed for concordance in relation to various histological and immunohistochemical parameters. A higher level of concordance was demonstrated for synchronous cases with the highest level seen for oestrogen receptor. It is likely that this is related to similar tumourogenic pathways occurring at equivalent exposure times to various environmental and hormonal influences, although, in a proportion of cases, inherited genetic factors may play a role.
    Breast Cancer Research and Treatment 07/2004; 85(3):255-61. · 4.47 Impact Factor
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    ABSTRACT: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.
    Journal of Clinical Pathology 07/2004; 57(7):695-701. · 2.44 Impact Factor
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    ABSTRACT: We have undertaken a pilot study to attempt to identify circulating carcinoma cells in a series of patients with advanced breast carcinoma, using reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA of epithelial specific antigens. Using this method to amplify mRNA of MUC1 and cytokeratin 7 (CK7) the sensitivity of the technique was demonstrated by means of diluted concentrations of "spiked MCF7" cells in whole blood, showing a detection limit of 1 in 10(6) (CK7) and 1 in 10(5) (MUC1). Positive results were obtained from the peripheral blood of all nine female patients with advanced breast cancer for CK7 and eight of the nine patients for MUC1. CK7 was however detected in five of 11 healthy controls (eight females, three males) and MUC1 in one of the 11 controls. None of the control group were positive for both CK7 and MUC1, in contrast to eight of the nine patients with advanced breast carcinoma who were positive for both markers. The RT-PCR method thus appears sufficiently sensitive to identify circulating tumour cells in peripheral blood samples from patients with advanced breast carcinoma. However a high proportion of false-positive results was seen in the control population. More extensive investigation is required before the technique is likely to be of benefit clinically.
    The Breast 03/2004; 13(1):35-41. · 2.49 Impact Factor

Publication Stats

8k Citations
1,020.65 Total Impact Points

Institutions

  • 1987–2008
    • University of Nottingham
      • • School of Molecular Medical Sciences
      • • Centre for Sports Medicine
      Nottingham, ENG, United Kingdom
    • The Queen's Medical Center
      Honolulu, Hawaii, United States
  • 1995–2007
    • Nottingham University Hospitals NHS Trust
      • Division of Histopathology
      Nottigham, England, United Kingdom
    • University of Western Australia
      Perth City, Western Australia, Australia
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia
  • 2003–2006
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1999–2004
    • Royal Adelaide Hospital
      Tarndarnya, South Australia, Australia
  • 1998–1999
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 1994
    • University College Dublin
      Dublin, Leinster, Ireland
  • 1986–1989
    • University of Wales
      • College of Medicine
      Cardiff, Wales, United Kingdom