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Biomedical subjects

I O Ellis

Publications and source records attributed to I O Ellis.

At least 91 records · Page 5Linked to original sources
PubMed2000

When have mammographic calcifications been adequately sampled at needle core biopsy?

AIMS: To determine if the number of flecks of calcification retrieved at stereotaxic core needle biopsy or the number of core samples obtained containing calcification are related to biopsy sensitivity, and to determine how many calcifications or cores containing calcification the radiologist should aim to retrieve when sampling mammographic microcalcification. MATERIALS AND METHODS: A retrospective review was performed of core specimen radiographs from 57 consecutive patients who had stereotaxic core needle biopsies of impalpable malignant microcalcifications without an associated mammographic mass. The total number of calcifications retrieved and the numbers of cores containing calcification were correlated with findings at core and surgical histology. RESULTS: Increasing retrieval of calcification elements visible on specimen radiography was associated with increasing sensitivity of the biopsy. Five or more flecks of calcium gave an absolute sensitivity of 100%. Increasing numbers of core samples obtained containing radiographically demonstrable calcification was also associated with increasing sensitivity. Three or more cores containing calcium resulted in a 100% absolute sensitivity for malignancy. CONCLUSION: To ensure adequate sampling of calcification at core biopsy, an optimum of either three or more cores containing calcium or five or more flecks of calcium in total is required. Achieving this target ensures a high pre-operative diagnosis rate for malignant microcalcifications.Bagnall, M. J. C. (2000). Clinical Radiology 55, 548-553.

Aged↗
PubMed2000

Ultrasound guided core biopsy of suspicious mammographic calcifications using high frequency and power Doppler ultrasound.

AIM: The pre-operative diagnosis of suspicious mammographic microcalcifications usually requires stereotactic needle biopsy. The aim of this study was to evaluate if high frequency 13 MHz ultrasound (HFUS) and power Doppler (PD) can aid visualization and biopsy of microcalcifications. MATERIALS AND METHODS: Forty-four consecutive patients presenting with microcalcifications without associated mammographic or palpable masses were examined with HFUS and PD. Ultrasound-guided core biopsy (USCB) was performed where possible. Stereotactic biopsy was carried out when US-guided biopsy was unsuccessful. Surgery was performed if a diagnosis of malignancy was made on core biopsy or if the repeat core biopsy was non-diagnostic. RESULTS: Forty-one patients (93%) had ultrasound abnormalities corresponding to mammographic calcification. USCB was performed on 37 patients. In 29/37, USCB obtained a definitive result (78.4%). USCB was non-diagnostic in 4/9 benign (44.4%) and 4/28 (14.3%) malignant lesions biopsied. The complete and absolute sensitivities for malignancy using USCB were 85.7% (24/28) and 81% (23/28), respectively. USCB correctly identified invasive disease in 12/23 (52.2%) cases. There was no significant difference in the presence of abnormal flow on PD between benign and malignant lesions. However, abnormal PD vascularity was present in 43.5% of invasive cancer and was useful in directing successful biopsy in eight cases. CONCLUSION: The combination of high frequency US with PD is useful in the detection and guidance of successful needle biopsy of microcalcifications particularly where there is an invasive focus within larger areas of DCIS.

Biopsy, Needle↗
PubMed2000

Digital imaging improves upright stereotactic core biopsy of mammographic microcalcifications.

AIM: This comparative study was carried out to assess the effect of using digital images compared to conventional film-screen mammography on the accuracy of core biopsy of microcalcifications using upright stereotactic equipment. MATERIALS AND METHODS: The biopsy results from a consecutive series of 104 upright stereotactic 14-gauge core biopsies performed with conventional X-ray (Group A) were compared with 40 biopsies carried out using stereotaxis with digital imaging (Group B). In all cases specimen radiography was performed and analysed for the presence of calcifications. Pathological correlation was then carried out with needle and surgical histology. RESULTS: The use of digital add-on equipment increased the radiographic calcification retrieval rate from 55 to 85% (P < 0.005). The absolute sensitivity of core biopsy in pure ductal carcinoma in situ (DCIS) cases rose from 34 to 69% (P < 0.03), with the complete sensitivity increasing from 52 to 94% (P < 0.005). For DCIS with or without an invasive component the absolute sensitivity rose from 41 to 67% (P = 0.052), while the complete sensitivity was 59% before and 86% after the introduction of digital imaging (P < 0.04). CONCLUSION: Digital equipment improves the performance of upright stereotactic core biopsy of microcalcifications, giving a significantly increased success rate in accurately obtaining calcifications. This leads to an improvement in absolute and complete sensitivity of core biopsy when diagnosing DCIS.

Adult↗
PubMed2000

c-erbB-4 protein expression in human breast cancer.

The Type 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4. Overexpression of the first two members is associated with poorer prognosis in patients with breast carcinoma. In this study we examined the expression of c-erbB-4 protein using the monoclonal antibody HFR-1. A total of 127 consecutive cases of primary operable invasive breast carcinoma presenting between 1975 and 1977 were studied. All patients were managed by simple mastectomy or conservation surgery with radiotherapy and no adjuvant therapy given. Long-term follow-up was maintained. Routine, formalin-fixed, paraffin-embedded tumour samples were used and sections were stained immunohistochemically using the Duet StreptABC method. Immunoreactivity was classified using a simple semi-quantitative scoring method. Protein expression was generally low but definite positive cytoplasmic, membranous and nuclear reactivity was identified in 58%, 41% and 25% of cases respectively. Expression at all three sites demonstrated significant inverse associations were histological grade. In addition, membrane accentuation correlated inversely with the Nottingham Prognostic Index (NPI), while cytoplasmic reactivity showed a positive association with c-erbB-3 expression. No significant associations were found with disease-free interval or survival. The results of this study demonstrate that higher levels of c-erbB-4 protein expression are associated with a more differentiated histological phenotype in contrast to the other members of the Type 1 family. Larger series with extended follow-up will be required to ascertain definitively the prognostic value of c-erbB-4 expression in breast carcinoma.

Adult↗
PubMed2000

Recommendations for HER2 testing in the UK.

Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin), which has recently been licensed for the treatment of metastatic disease. This necessitates a test based on archival material. The preferred analyses are immunohistochemistry with fluorescent in situ hybridisation (FISH) as a follow up test for ambiguous results. Guidelines have been developed for standardised, well controlled procedures for the provision of reliable results. A group of three reference laboratories has been established to provide advice, quality assurance, and materials, where needed.

Biomarkers, Tumor↗
PubMed1999

BRCA1 expression levels predict distant metastasis of sporadic breast cancers.

The role of BRCA1 in progression of sporadic breast cancers has to date been equivocal, although preliminary studies on small numbers of samples have suggested an association between expression levels of this gene and acquisition of an invasive phenotype. We have further reasoned that loss of oestrogen receptor positivity may have a detrimental effect on BRCA1 expression. In order to test this hypothesis and extend earlier investigations we have applied a sensitive RT-PCR procedure to determine the associations between BRCA1 expression and a variety of clinical parameters in a sample cohort derived from sporadic breast tumour specimens. We have established that BRCA1 and ER mRNA expression are closely associated (p=0.013), indicating a possible functional relationship between these 2 genes. We have further identified an association between low levels of BRCA1 expression and acquisition of distant metastasis in sporadic disease (p=0.019). In light of our findings, we suggest that suppression of BRCA1 has a role to play in progression of a significant fraction of sporadic breast cancers and may additionally prove to be a useful, novel, prognostic marker for this disease type.

BRCA1 Protein↗
PubMed1999

Endocrine response and resistance in breast cancer: a role for the transcription factor Fos.

We have previously demonstrated that elevated Fos expression may be important in de novo endocrine resistance in breast cancer. However, changes in Fos expression during endocrine response and subsequently on acquisition of resistance are unknown. This study immunocytochemically monitors Fos protein within sequential biopsies from primary human breast cancer patients obtained pre-treatment (T1), during tamoxifen therapy (T2, T3) and on disease progression (T5), examining in parallel proliferation [i.e., MIBI (Ki67) immunostaining, mitotic activity], cellularity and endocrine response. Significantly diminished Fos, proliferation and cellularity were observed after 6 weeks of therapy in patients exhibiting a better quality and/or duration of response, while modest Fos increases and a maintained proliferation and cellularity were seen in poorer responders. Decreases in Fos, proliferation and cellularity at 6 months similarly hallmarked better responders. We confirmed a significant association between de novo resistance and elevated Fos and proliferation. Additionally, however, these parameters increased at the time of disease relapse over pre-treatment and "on therapy" values. Our data indicate that tamoxifen response involves a reduction in both tumor cell proliferation and cell survival, potentially entailing diminished Fos protein expression in better-responding patients. Our data are also supportive of elevated Fos expression being involved in the departure from endocrine control inherent in both primary and acquired resistance.

Aged↗
PubMed1999

An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer.

This study examines the expression of the cell-cell adhesion molecules E-cadherin and its associated proteins, the catenins and the matrix-cell adhesion molecules beta1- and alpha2-integrins, in primary invasive breast carcinoma. Expression was assessed immunohistochemically on frozen sections by semi-quantitative scoring of the intensity and proportion of immunoreactivity in 55 cases. Associations with each other and with other histological and prognostic features and survival were sought. There was a significant association between loss of E-cadherin expression and loss of alpha- and beta/gamma-catenin immunostaining. In 20 per cent of cases, membranous immunoreactivity with E-cadherin antibody was absent. Absent cytoplasmic expression of alpha- and beta/gamma-catenins was seen in 24 and 22 per cent of breast cancers, respectively. The intensity of reactivity with E-cadherin showed a significant association with histological grade (p=0.002) and tumour type (p<0.001). Lobular carcinomas frequently showed loss of expression of E-cadherin, as reported elsewhere; loss of catenin expression was also found in these tumours. alpha-catenin intensity also showed a relationship with grade (p=0.008) and with oestrogen receptor (ER) status (p=0.006). beta/gamma-catenin expression was not associated with other known prognostic factors. Forty-nine per cent and 42 per cent of cases showed no membrane immunostaining with beta1- and alpha2-integrin, respectively, and co-ordinated loss of beta1- and alpha2-integrin expression was found. Both beta1- and alpha2-integrin expression were associated with histological grade (p=0.003 and p=0.031, respectively) and beta1 immunoreactivity with tumour type (p=0.010). None of the variables examined showed a statistically significant association with tumour size or lymph node stage, or with overall survival, although a trend was seen (p=0.087) towards poorer survival of patients with tumours with absent or weak expression of beta1-integrin. The expression of these markers is of biological interest, but appears to be of little additional use in predicting clinical behaviour.

Adult↗
PubMed1999

p21(WAF1) expression and endocrine response in breast cancer.

An immunocytochemical assay for the p53-regulated protein product of the WAF1/Cip1 gene, p21(WAF1) (p21), was developed and applied to archival primary breast tumour material from 91 patients whose subsequent recurrent disease was treated with assessable courses of endocrine therapy. Nuclear localization of p21 protein was observed in 76 (82.4 per cent) cases. Status cut-offs were established and 29 (31.9 per cent) were deemed negative, 39 (42.9 per cent) weakly positive, and 23 (25.3 per cent) strongly positive. p21 status was inversely correlated with p53 protein (p=0.047) but did not relate to oestrogen receptor (ER) status, response to endocrine therapy, or time to further disease progression (TTP). Highly p21-positive patients had a significantly improved overall survival time (p=0. 020). Co-assessment of p21 and p53 subgroups revealed p21+/p53- patients to have good survival characteristics, whilst p21-/p53+ patients did poorly (p=0.008). The p21-/p53- patients overall did intermediately well, but Ki67-defined cellular proliferation analysis of these revealed two subclasses: those with high proliferation and poor survival times resembling the p21-/p53+ phenotype, and those with less proliferative tumours with good survival, similar to the p21+/p53- group. The significance of these results is discussed in the light of recent research concerning the role of p21 and p53 in breast cancer aetiology.

Adult↗
PubMed1999

Immunohistochemical analysis reveals a tumour suppressor-like role for the transcription factor AP-2 in invasive breast cancer.

This paper describes the generation and characterization of a monoclonal antibody specific for two members of the AP-2 family of transcription factors, AP-2alpha and AP-2beta, and its subsequent application to archival primary breast tumour material. Nuclear localization of AP-2 was found in all expressing cases, but in general levels of immunostaining were low, with only 17 per cent of the 86 tumours examined showing very high expression levels. Nevertheless, data analysis of the whole patient series allowed the identification of significant relationships between levels of AP-2 and other important breast markers. Thus, expression of AP-2alpha/beta was found to correlate significantly with expression of both ER ( p=0.036*) and the universal cell-cycle inhibitor p21(cip) ( p=0.03*), but was inversely related to levels of the proto-oncogene ErbB2 ( p=0.008*). AP-2-positive tumours also showed a low rate of proliferation, with significantly reduced mitotic count and a lower tumour grade. There was no significant relationship with clinical parameters, but samples with adjacent normal tissue indicated that loss of the AP-2 marker was associated with disease progression from normal breast through to invasive disease. This was confirmed by examining separate series of pure normal and pure DCIS samples, both of which expressed significantly higher levels of AP-2 ( p=0.0001* in each case) than the invasive tumours. Overall, these findings implicate AP-2alpha/beta as having a role akin to that of a tumour suppressor in breast cancer.

Antibodies, Monoclonal↗
PubMed1999

Bilateral breast carcinomas: do they have similar mammographic features?

AIMS: This study compared the mammographic appearance, site and histological features of synchronous and metachronous bilateral breast carcinomas. METHODS: Site, type of abnormality and background pattern seen on the diagnostic mammograms of 63 women with bilateral breast carcinoma were compared. The histological type and grade of all the carcinomas were verified by histological review. RESULTS: There was a tendency for the contralateral tumour to have similar mammographic features to those of the initial tumour. In patients in whom the first carcinoma was visible purely as a mass, the contralateral carcinoma had a similar appearance in 82% (P < 0.001). When the original tumour showed mammographic calcification the contralateral tumour did so in 65% (P< 0.001). Normal mammography or calcification alone were seen almost exclusively in women with a dense background pattern (100% and 92% respectively) while masses and calcification with masses were seen in women with dense and fatty patterns (58% and 35% dense respectively). When the mammographic site of the contralateral tumour was compared with that of the first tumour no significant correlation could be demonstrated. There was a significant trend for contralateral carcinomas to be of the same histological grade (P < 0.005) but not histological type. CONCLUSIONS: Contralateral carcinomas often have a similar mammographic appearance to the first tumours. Two factors may be responsible: (i) the tendency for contralateral carcinomas to be of the same histological grade and (ii) the influence of mammographic background pattern on the radiological appearance of breast carcinoma. This knowledge may assist in the interpretation of follow-up mammography in patients with a previous breast carcinoma.

Adult↗
PubMed1999

Mammographic features of ductal carcinoma in situ (DCIS) present on previous mammography.

AIM: To review previous mammograms of women found later to have DCIS and identify features which may have been missed or misinterpreted as benign. METHODS: The previous mammograms of 50 women who developed DCIS were analysed. The mammographic features at diagnosis and on the prior mammograms were compared. RESULTS: 11 (22%) of the previous mammograms were in retrospect abnormal; 5 (45%) of these had previously been assessed for the abnormality. All showed microcalcification. The following features were commoner at diagnosis than on previous films; rod shaped calcification (64 vs. 27%, P = 0.03) and a ductal distribution of calcification (76 vs. 45%, P = 0.05). Predominantly punctate calcification (64 vs. 12%, P = 0.001) and less than 10 calcifications in the cluster (54 vs. 24%, P = 0.05) were more common on the previous films. No difference was found in the frequency of granular calcification, branching calcification, irregularity in density, size or shape of calcification between the two groups. CONCLUSION: Features of DCIS missed on previous mammography include small cluster size, less than 10 calcifications in the cluster, the absence of rod shaped calcifications, the absence of a ductal distribution and the presence of predominantly punctate calcification. Features frequently seen both at diagnosis and on previous films which might have allowed earlier diagnosis were granular calcifications which vary in size, density and shape in an irregularly shaped cluster. Focal clustered calcification deserves aggressive investigation.

Adult↗
PubMed1999

The prognosis of small primary breast cancers.

The Nottingham Prognostic Index (NPI) is an integrated prognostic index used to predict patient survival for women with invasive breast cancer. The index is based on invasive tumour size, histological lymph node stage and tumour grade. The value of such an index has been questioned in small invasive breast cancers and it has been suggested that size is the only necessary prognostic determinant. The aims of this study were to determine the extent of regional lymph node involvement and survival in women with small invasive breast cancers and to assess the value of the NPI. Between 1976 and 1994, 2684 women aged < or = 70 years were treated for primary operable invasive breast cancers of < or = 5 cm in maximum diameter, of which 318 measured < or = 1 cm. Follow-up data were evaluated to determine histological factors important in predicting survival outcomes in women with cancers < or = 1 cm in diameter and comparing their survival according to the NPI with all women treated for primary operable breast cancers < or = 5 cm in maximum diameter. Histological lymph node involvement was demonstrated in 56/318 (18%) of cancers of < or = 1 cm in diameter. Significant survival differences were demonstrated for small breast cancers according to lymph node stage, vascular invasion and histological tumour grade. Only lymph node stage and histological tumour grade were independent prognostic indicators using a multivariate Cox model. The survival curves for small tumours stratified by the NPI were similar to those of cancers up to 5 cm in diameter. The results indicate that lymph node staging and histological grading are still important prognostic determinants for breast cancers < or = 1 cm in diameter. An axillary node staging procedure should be performed for all invasive breast cancers < or = 1 cm in diameter. The NPI remains relevant for small breast cancers.

Adult↗
PubMed1999

Anti-gonadotrophin releasing hormone antibodies inhibit the growth of MCF7 human breast cancer xenografts.

The human breast cancer cell line (MCF7) was established as xenografts in intact female nude mice. Xenografts did not require oestrogen supplementation for growth, although oestrogen supplementation caused more rapid tumour growth. GnRH Pharmaccine is an immunogen composed of gonadotrophin releasing hormone (GnRH) linked to diphtheria toxoid. Anti-GnRH antibodies purified from the serum of rabbits immunized with GnRH Pharmaccine, were used to passively immunize nude mice. In mice treated with anti-GnRH antibodies, xenograft growth was significantly inhibited relative to controls (median times of 71 and 29 days respectively taken for tumours to attain a predetermined cross-sectional area of 200 mm2, P < 0.001). The inhibition of tumour growth achieved by anti-GnRH antibodies was not significantly different from that produced by the anti-oestrogen, tamoxifen (59 days). Ovarian/uterine weights were reduced by 61% (P < 0.001) in anti-GnRH antibody-treated animals compared with controls. Histologically there was underdevelopment and atrophy of the reproductive organs. Serum levels of both oestrogen and luteinizing hormone were reduced by treatment with anti-GnRH antibodies (to 24.9% and 53% respectively of levels in controls, both P = 0.04). It is postulated that one of the mechanisms by which anti-GnRH antibody treatment inhibits tumour growth is indirectly, by reducing serum oestrogen levels.

Animals↗
PubMed1999

Clinical and histological predictors of contralateral breast cancer.

AIMS: Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast. The purpose of this study was to assess the annual incidence of metachronous contralateral breast cancer (CBC) and to identify factors that predict for its development. METHODS: A retrospective study was performed on 3211 women aged </=70 years treated for primary operable breast cancer between 1975 and 1995. RESULTS: Eighty-three developed CBC prior to locoregional or distant recurrence from the first primary. The clinical incidence of CBC was 6.4 per 1000 women years, three to four times the risk of occurrence of breast cancer in the general female population (or a risk of six to eight times to the remaining breast). Strong family history, age of onset <50 years and lobular histology were significant factors predicting for CBC in univariate and multivariate models. Other clinical factors (previous hormone therapy, chemotherapy, radiotherapy) or histological factors (DCIS, invasive tumour size, grade, vascular invasion, lymph node and oestrogen receptor status) were not significant predictors for CBC. CONCLUSIONS: In women previously treated for primary operable breast cancer, early age of onset and a strong family history are predictors for the subsequent development of metachronous CBC. Ipsilateral mastectomy with contralateral prophylactic mastectomy with or without immediate breast reconstruction is a reasonable option for a young woman diagnosed with breast cancer and who has a strong family history, particularly if the cancer has histological features suggesting a good prognosis.

Aged↗
PubMed1999

Severe hypoglycaemia caused by raised insulin-like growth factor II in disseminated breast cancer.

A 60 year old woman with disseminated ductal carcinoma of the breast developed non-islet cell tumour induced hypoglycaemia (NICTH). The concentrations of the two insulin-like growth factors, IGF-I and IGF-II, were < 2 nmol/l and 94.1 nmol/l, respectively. The IGF-II to IGF-I ratio was > 47 (normal < 10). Insulin (< 3 mu/l) and C peptide (< 100 pmol/l) were both undetectable.

Adenocarcinoma, Papillary↗