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C W Elston

Publications and source records attributed to C W Elston.

At least 73 records · Page 4Linked to original sources
PubMed1995

A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples.

We describe a method for the immunocytochemical assessment of estrogen receptor (ER) status on routinely processed, formalin-fixed tissue using a recently developed commercially available monoclonal antibody (Dako 1D5) with a microwave antigen retrieval technique. A series of 90 cases of human breast carcinoma was analyzed and the staining was assessed using a semiquantitative microscopic scoring method and by assessment of the percentage of nuclei showing positive staining. The results were compared with assessment using another commercially available antibody (Abbott H222) and with clinical response to tamoxifen therapy. Direct comparison of the paired sets of H scores and the percentage of positively stained nuclei using the two different techniques showed a significant correlation. By assigning an arbitrary cut-off for positivity of H score = 50, assessment of ER status using DAKO 1D5 antibody was found to correlate with response to tamoxifen therapy with a sensitivity of 90% and a specificity of 51%, similar to values in previous studies using other methods. We conclude that assessment of ER status using this new antibody and technique gives accurate results on routinely processed, formalin-fixed tissue and may be used as an alternative to other methods.

Adult↗
PubMed1995

Assessment of angiogenesis in breast carcinoma: an important factor in prognosis?

Recent evidence suggests that angiogenesis, as assessed by vascular density, may be an independent prognostic factor in breast carcinoma. The authors chose to examine this hypothesis further using two different methods, both using an immunohistochemical technique to assess vascularity. In the first, tissue sections from 93 patients with human breast carcinoma were immunostained for the endothelial antigen CD 34. Fields were selected at random in sections stained with the monoclonal antibody QBEnd/10, and both the number of blood vessels and percentage of endothelial cells per unit area measured using an interactive image analysis system (SEESCAN). In the second, an additional 72 patients were added and the 165 sections immunostained for CD31 (PECAM 1) using the monoclonal antibody JC 709. The area of highest vascular density was then identified and measured. A statistically significant correlation was found between percentage endothelial area and tumor type (P < .03) using the first method, and, for lymph node-negative patients only, between vascular density and tumor type (P < .02) using the second method. There was no correlation with lymph node status, recurrence, distant metastases, or overall survival using either method (minimum follow-up 12 years). The authors conclude that the evaluation of tumor angiogenesis using these methods does not provide additional prognostic information in this group of patients.

Antibodies, Monoclonal↗
PubMed1995

Safe selection criteria for breast conservation without radical excision in primary operable invasive breast cancer.

In a previous series from this unit of 263 women with primary operable breast cancer treated by macroscopic lumpectomy and breast irradiation, local recurrence was high. An audit at a median follow up of 36 months showed 56 (21%) ipsilateral breast recurrences. Eighteen of these recurrences were aggressive and uncontrolled. Multivariate analysis shows patient age, lymphovascular invasion, tumour size and nodal status to be predictive of local recurrence (Locker AP, et al., Br J Surgery 1989, 76, 890-894). New selection criteria for breast conservation were defined based on these data and also on securing an adequate clear margin of excision. In a subsequent prospective series of 275 women fulfilling these criteria, 6 women (2.2%) developed ipsilateral breast recurrence at the same median follow up of 36 months. In none was this uncontrolled and aggressive. Breast conservation, without radical excision, is safe as long as the selection criteria described are followed.

Adult↗
PubMed1995

Assessment of the new proliferation marker MIB1 in breast carcinoma using image analysis: associations with other prognostic factors and survival.

The 'growth fraction' of tumours can now be assessed on paraffin sections of tissues using the monoclonal antibody MIB1 by a microwave antigen retrieval technique. The MIB1 labelling index was studied using a CAS 200 image analyser in 177 tumours from women with primary operable breast carcinoma in whom long-term follow-up data were known. Statistical analysis showed a strong association between the MIB1 labelling index and histological grade (P < 0.001), tumour size (P = 0.002), tumour type (P < 0.001) and also patient survival (P < 0.001). No association with lymph node stage (P = 0.974) or regional recurrence (P = 0.185), the presence or absence of distant metastases (P = 0.418), patient age (P = 0.309), menopausal status (P = 0.181) or oestrogen receptor status (P = 0.401) was found in this group of patients. In multivariate analysis for survival, when histological grade, lymph node stage and tumour size were included as well as the MIB1 labelling index, each was found to be of independent significance. If histological grade was not included, MIB1 replaced it as the most important variable predicting for survival in this group of patients. The results suggest that the tumour growth fraction, as assessed by the MIB1 labelling index, is an important predictor of survival.

Antibodies, Monoclonal↗
PubMed1995

Metallothionein expression in human breast cancer.

Metallothioneins are ubiquitous low molecular weight proteins characterised by high cysteine content and affinity for binding heavy metals. Abnormal metallothionein function and expression have been implicated in various disease states, including neoplasia. The aim of this study was to investigate metallothionein expression in human breast carcinoma. Sections of routinely fixed and processed blocks of tumour from 100 consecutive cases of primary operable breast carcinoma were stained for metallothionein using a recently developed monoclonal antibody and a standard immunohistochemical technique. Expression was scored on the basis of microscopical assessment of percentage of tumour cells staining. One patient was lost to follow-up and excluded from the study. A significant association (P < 0.0001) was observed between metallothionein expression and tumour type, with low levels being observed in tumours of good prognostic type. There was also a significant association with local recurrence (P < 0.02) and a significant difference (P < 0.02) in both survival and disease-free interval between tumours showing low and high levels of expression, the latter indicating a poor prognosis. No relationship was observed with patient age, tumour size, lymph node stage, histological grade, vascular invasion, menopausal status or oestrogen receptor status. The assessment of metallothionein expression in human breast cancer appears to provide prognostic information and may have important implications for understanding its development.

Breast Neoplasms↗
PubMed1995

The assessment of multiple variables on breast carcinoma fine needle aspiration (FNA) cytology specimens: method, preliminary results and prognostic associations.

We have assessed the multiple biological variables on breast carcinoma FNA specimens using a Cytoblock technique. The growth fraction (MIB1), oestrogen receptor (ER), progesterone receptor (PR), p53 mutant protein, c-erbB-2, epidermal growth factor receptor (EGFR), NCRC11/epithelial membrane antigen (EMA) and DNA plopidy were examined. Objective quantification using image analysis (CAS 200) was applied as appropriate. Fifty cases were examined in this preliminary study. Excellent correlation between the Cytoblock preparations and parallel tissue sections was seen. Of the cancers, 81% were aneuploid with only 19% diploid in character, but 67% of the carcinomas were of histological grade 3. The mean nuclear area staining with MIB1 was 31.3% and with ER was 26.7%. Twenty-four percent (24.1%) of the nuclear area showed immunoreactivity with PR. Significant EGFR and EMA, respectively. A significant association between histological grade of the resected tumours and both MIB1 (P = 0.04) and EGFR (P = 0.02) expression in the Cytoblock samples was seen. p53 (P = 0.03) and EGFR (P = 0.01) immunoreactivity showed an association with tumour size. EGFR (P = 0.04) immunostaining also showed a relationship with the lymph node status of the patient. The technique is, we believe, a useful one for the assessment of multiple variables on breast cytology specimens; these preliminary data suggest that some of these may be useful in predicting prognosis in breast cancer patients.

Analysis of Variance↗
PubMed1995

Phyllodes tumours of the breast: a clinicopathological review of thirty-two cases.

We have reviewed the histological features and clinical outcome in 32 women with phyllodes tumours of the breast diagnosed in Nottingham between 1975 and 1990. We assessed 23 tumours as histologically benign, four as borderline and five as malignant. After clinical follow up for periods ranging from 36 months to 221 months (median 135 months), six of 23 benign tumours have recurred locally; in all these cases the original tumours had been incompletely excised. There were no recurrences amongst 10 benign tumours in which excision had been complete. Benign tumours which recurred showed a tendency to greater stromal cellularity and more pronounced stromal overgrowth than incompletely excised lesions which did not recur, but these differences were not statistically significant. The recurrent tumours resembled the respective original lesions histologically, except in one case in which two local recurrences were histologically malignant. The recurrent tumours were controlled by further excision or mastectomy in all cases and none have metastasized. All four borderline tumours were completely excised at initial surgery and none have recurred or metastasized. One of the five malignant tumours recurred within two months of incomplete excision, with widespread infiltration of the chest wall, although the patient died of unrelated causes. The other four malignant tumours have not recurred. We conclude that presence of tumour at the margins of the excised specimen is the major determinant of local recurrence in phyllodes tumours and that the histological features are of secondary importance. These findings are discussed in relation to other published series in the literature.

Adult↗
PubMed1995

Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma.

In a study of 1529 patients with primary operable breast carcinoma we have assessed the effect of applying both histological grade and tumour type to determine their comparative value as prognostic factors in human breast cancer. The prognostic group the patient was placed in, based on histological type alone, was less accurate than using grade and type together for many tumours. The importance of performing histological grading of ductal/no special type carcinoma (50% of the women in this series) is confirmed in this series. The 10-year-survival varied from 76% for women with grade 1 carcinoma to 39% for those with grade 3 tumours. Some of the 'special types' of breast carcinoma including tubular, tubulo-lobular, invasive cribriform and grade 1 mucinous carcinomas behaved as would be predicted, with a greater than 80% 10-year-survival in this series. Others, including grade 2 mucinous carcinomas, however, behaved less well with a 60% to 80% 10-year-survival. Indeed, many of the histological tumour types including tubular mixed, ductal/no special type, mixed ductal with special type and lobular carcinomas of classical, solid or mixed types showed a variation in behaviour that could not be predicted by typing alone. Histological grade and tumour type, when used together, more accurately predicted prognosis. In multivariate analysis of a larger group of 2658 cases of primary breast carcinomas (including the 1529 study cases) when histological grade, lymph node status and tumour size were entered, grade was the most important factor in predicting for survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Mammographic features of invasive lobular and invasive ductal carcinoma of the breast: a comparative analysis.

The mammographic appearances of 86 invasive lobular carcinomas were compared with those of 86 invasive ductal carcinomas of no special type matched for age, size and stage. There was no significant difference in the frequency of a mammographic abnormality consistent with malignancy between the lobular carcinoma (90%) and ductal carcinoma (96%) groups. A spiculate mass was the commonest feature in both groups (69% and 63%, respectively). There were no differences in the imaging features of masses in the two groups. In the lobular carcinoma group any mammographic abnormality was more likely to be seen on only one view and calcifications were less frequently observed. Multiple lesions were more frequent in the ductal carcinoma group. However, although these differences appeared to reach statistical significance, as they were only apparent in a study with a large number of comparisons, it is unlikely that these differences are practically significant. Analysis of the lobular invasive group failed to demonstrate any significant differences in the imaging features of the classical and mixed sub-types, a spiculate mass being the most common single abnormality in both. No mammographic differences of practical use to distinguish invasive lobular from invasive ductal carcinoma of no special type were demonstrated.

Adult↗
PubMed1994

Local recurrence after simple mastectomy.

A retrospective study was carried out to determine the clinical significance of local recurrence after simple mastectomy and node biopsy for primary operable breast cancer, without postoperative irradiation or systemic adjuvant therapy. Local recurrence was defined as a histologically proven lesion in or deep to the mastectomy skin flaps. A total of 966 patients with a median follow-up of 7 years were reviewed. Of these, 223 (23 per cent) developed local recurrence but half the tumours were small single lesions; 70 women had multiple discrete lesions and 21 diffuse carcinomatous dermal infiltration. Local recurrence showed significant associations with tumour grade, nodal status and the presence of lymphovascular invasion in the primary tumour. A predictive index containing these three variables was constructed. Adjuvant irradiation of the flaps is recommended for patients with high scores; such women would otherwise have a 39 per cent chance of developing local recurrence by 5 years. Different types of local recurrence have different chances of responding to local therapy: 13 per cent of single local recurrences, 32 per cent of multiple spot recurrences and 70 per cent of the diffuse type failed to respond to local therapy. Local recurrence predicts reduced patient survival.

Aged↗
PubMed1994

Biological factors of prognostic significance in locally advanced breast cancer.

The biological features of tumour type, histological grade, vascular invasion, mitotic index, DNA index, and oestrogen receptor (ER) and progesterone receptor (PgR) status have been investigated as prognostic factors in primary operable breast cancer. We have studied these 7 factors in locally advanced primary breast cancer (LAPC): these patients have occult metastases at presentation. Of 60 consecutive patients presenting with locally advanced disease, 36 were treated initially with Tamoxifen and 24 by radiotherapy. Treatment failure was followed by cross-over to the other therapy. All patients were assessed for response in the primary tumour; external review of response was obtained. Survival was compared using the generalised Wilcoxon test. Response to therapy correlated significantly with histological grade (p = 0.02), ER (p = 0.02), PgR status (p = 0.02), mitotic index (p = 0.01), and tumour ploidy (p = 0.04). Survival from initial therapy correlated significantly with ER (p = 0.01) and PgR status (p = 0.04). Histological grade, mitotic index, tumour ploidy, and ER and PgR status of the primary tumour predict response and prognosis in patients with locally advanced (stage III) breast cancer.

Aged↗
PubMed1994

Consistency of histopathological reporting of breast lesions detected by screening: findings of the U.K. National External Quality Assessment (EQA) Scheme. U. K. National Coordinating Group for Breast Screening Pathology.

The aim of the scheme was to determine consistency of histopathological reporting in the United Kingdom National Breast Screening Programme. This external quality assessment scheme involved 51 sets of 12 slides which were circulated to 186-251 pathologists at intervals of 6 months for 3 years. Participants recorded their diagnoses on standard reporting forms, which were submitted to the U.K. National Cancer Screening Evaluation Unit for analysis. A high level of consistency was achieved in diagnosing major categories of breast disease including invasive carcinoma and the important borderline lesions, radial scar and ductal carcinoma in situ (DCIS), the latter exceeding a national target set prior to the onset of the scheme. Atypical hyperplasia (AH) was reported with much less consistency although, where it was the majority opinion, over 86% of diagnoses were of benign disorders and only 14% were of DCIS. Inconsistency was encountered in subtyping and measuring DCIS, the former apparently due to current uncertainties about classification and the latter to poor circumscription, variation in size in different sections and merging with zones of AH. Reporting prognostic features of invasive carcinomas was variable. Measurement of size was achieved with adequate consistency except in a small number of very poorly circumscribed tumours. Grading and subtyping were inconsistent although the latter was not specifically tested and will be the subject of future study. Members of the National Coordinating Group achieved greater uniformity than the remainder of the participants in all diagnostic categories, but both groups experienced similar types of problem. Our findings suggest that participation in the scheme improves diagnostic consistency. In conclusion, consistency in diagnosing invasive carcinoma and radial scar is excellent, and good in DCIS, but improvements are desirable in diagnosing atypical hyperplasia, classifying DCIS and reporting certain prognostic features of invasive tumours. Such improvements will require further research, the development of improved diagnostic criteria and the dissemination of clearer guidelines.

Breast↗
PubMed1994

Oestrogen-regulated genes in breast cancer: association of pLIV1 with lymph node involvement.

In order to isolate markers of oestrogen responsiveness in breast cancer, we have cloned a number of oestrogen-regulated genes. Two of these, pLIV1 and pLIV2 (pS2), have been shown to be predominantly expressed in oestrogen receptor (ER)+ tumours. In this study, we examined their expression in relation to various clinical and histopathological features of breast cancer, and showed that pLIV1, but not pS2, is significantly associated with lymph node involvement (P < 0.01), while pS2 is more frequently observed in premenopausal patients (P < 0.05). Subdivision of the pLIV1 data by ER and nodal status of the tumour identified a highly significant association between pLIV1 expression and lymph node involvement in ER-positive disease, with 15/24 (63%) ER+ pLIV1+ tumours showing nodal involvement. Conversely, 20/23 (87%) ER+ pLIV1- patients were lymph node-negative (P < 0.001). Subdivision of the pS2 data by ER status did not reach significance. The application of pLIV1 as a marker of lymph node involvement was further exemplified in small tumours (< < 2 cm), where 11/12 (92%) lymph node-positive patients expressed pLIV1, while 17/22 (77%) node-negative patients were pLIV1 negative (P < 0.001). Similarly, pLIV1 expression identified lymph node involvement in moderately differentiated tumours (P < 0.01), but was independent of vascular invasion. pLIV1 may, therefore, represent a candidate gene for metastatic spread in ER+ breast cancer.

Breast Neoplasms↗
PubMed1994

Pathological-radiological correlations in benign lesions excised during a breast screening programme.

Benign biopsies are an inevitable part of any screening programme. They add significantly to the psychological and financial 'cost' of screening and so should be kept to a minimum. To identify possible means of reducing these false positive results we have reviewed the mammographic features of 108 benign lesions removed during prevalent round screening and correlations were sought with the pathological findings. The commonest mammographic abnormalities leading to benign biopsy were non-comedo type suspicious calcification (29%), poorly defined mass (21%), architectural distortion (19%) and a well defined mass (18%). The histological correlates were: non-comedo type suspicious calcification (fibrocystic change 60%, sclerosing adenosis 35%, and radial scar/CSL 13%), poorly defined masses (fibrocystic change 37%, fibroadenomas 37%, and sclerosing adenosis 25%) and architectural distortion (radial scar/CSL 61% and fibrocystic change 26%). Methods of reducing screening provoked benign biopsies are discussed.

Breast↗
PubMed1994

Correlations between the mammographic features of ductal carcinoma in situ (DCIS) and C-erbB-2 oncogene expression. Nottingham Breast Team.

PURPOSE: C-erbB-2 oncogene expression is found in 60% of DCIS cases. C-erbB-2 expression in DCIS has been shown to correlate with comedo subtype, large cell size, lymphoid infiltrate, nuclear pleomorphism, multinucleation and high mitotic rate. These findings have led to the suggestion that the subgroup of DCIS that expresses c-erbB-2 may be a biologically definable category with prognostic significance. The purpose of this study was to identify any differences in the mammographic appearances between DCIS which expresses c-erbB-2 and DCIS that does not express this oncogene. MATERIALS AND METHODS: C-erbB-2 staining characteristics and preoperative mammograms were available for review in 126 patients with pure DCIS. All the mammograms were reviewed by a radiologist knowing the patient had DCIS but without any further pathological or immunohistochemical information. RESULTS: C-erbB-2 positive DCIS showed the following features more commonly than c-erbB-2 negative disease: calcification (65 of 71 (92%) vs 28 of 39 (72%), P < 0.01), ductal distribution of calcification (51 of 65 (78%) vs 16 of 28 (57%), P < 0.05), rod-shaped calcification (53 of 65 (82%) vs 15 of 28 (54%), P < 0.01) and granular calcification (63 of 65 (97%) vs 24 of 28 (86%), P < 0.05). C-erbB-2 negative DCIS more commonly showed an abnormal mammogram without calcification than c-erbB-2 positive disease (11 of 39 (28%) vs 6 of 71 (8%), P < 0.01). CONCLUSION: We have demonstrated significant differences in the mammographic features of c-erbB-2 positive and negative disease. As c-erbB-2 expression has been shown to correlate with aggressive histological features, the differences in the mammographic appearances between c-erbB-2 positive and c-erbB-2 negative DCIS may be of practical value.

Biomarkers, Tumor↗
PubMed1994

Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up.

The invasion of vascular spaces (lymphatic and/or blood vessel) by tumour, as assessed on routine haematoxylin and eosin sections, was investigated in a consecutive series of 1704 women with primary operable invasive breast carcinoma. Strict morphological criteria were used. Patients were under 70 years of age and received definitive surgery with no adjuvant systemic therapies. Information from regular follow-up (range 3-17 years) was recorded on to a computer database. Definite vascular invasion was seen in 22.8% of cases and concurrence between pathologists was high. In univariate analyses, vascular invasion was strongly associated with lymph node stage (P < 0.0001), tumour size (P < 0.0001), histological grade (P < 0.0001) and type of tumour (P < 0.0001). In multivariate analyses vascular invasion was of independent prognostic significance for both survival and for local recurrence of tumour; patients with tumours showing no vascular invasion had a significant survival advantage and a reduced risk of local recurrence. No association with oestrogen receptor status or menopause status was seen. The results confirm that histological assessment of vascular invasion provides independent prognostic information in primary operable breast carcinoma which may be helpful in making clinical decisions.

Aged↗