PubMed Health⌕ Search

Biomedical subjects

I O Ellis

Publications and source records attributed to I O Ellis.

At least 73 records · Page 4Linked to original sources
PubMed2001

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty.

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty Although several articles on the methodological aspects of mitotic counting have been published, the effects of macroscopic sampling and tumour heterogeneity have not been discussed in any detail. In this review the essential elements for a standardized mitotic counting protocol are described, including microscopic calibration, specific morphological criteria, macroscopic selection, counting procedure, effect of biological variation, threshold, and the setting of an area of uncertainty ('grey area'). We propose that the use of a standard area for mitotic quantification and of a grey area in mitotic counting protocols will facilitate the application of mitotic counting in diagnostic and prognostic pathology.

Data Interpretation, Statistical↗
PubMed2001

Predicting invasion in mammographically detected microcalcification.

AIM: To identify pre-operative factors which predict presence of invasive disease within mammographically detected malignant microcalcification. MATERIALS AND METHODS: A retrospective analysis was undertaken of 116 serial stereotactic core needle biopsies (SCNBs) performed on malignant mammographic calcification. Final surgical pathology was correlated with pre-operative features (clinical, radiological and core histology) in an attempt to predict the presence of an invasive component. RESULTS: Thirty-eight clusters contained invasive carcinoma. The sensitivity of SCNB for invasion was 55%. Clinical features, calcium morphology and cluster size were not shown to be predictive of invasive disease. Ductal carcinoma in situ (DCIS) of high grade on core histology and increasing number of calcifications were predictive of increased risk of invasion (high grade core biopsy DCIS and > 40 calcifications 48% invasive at surgical histology; high grade core biopsy DCIS and < 40 calcifications 15% invasive; non-high grade core biopsy DCIS 0% invasive). CONCLUSIONS: Identification of those clusters diagnosed as DCIS by percutaneous biopsy which are likely to harbour an invasive component is possible. It would seem reasonable to consider staging the axilla at therapeutic surgery in these patients.

Adult↗
PubMed2001

Prognostic and predictive factors in primary breast cancer and their role in patient management: The Nottingham Breast Team.

Breast cancer is the most common carcinoma amongst women in the Western world, yet there are now encouraging signs that improvements in mortality may be a realistic target. Increasing breast awareness amongst women due to better health education can lead to earlier clinical detection. In addition, population screening with mammography can achieve a significant improvement in survival. With significant changes in the range and type of therapeutic options available for patients with breast cancer, there is now a trend towards patients exercising their right in management and therapeutic decisions. All these developments highlight the increasing importance of prognostic and predictive factors in the management of patients with breast cancer. In this review we will discuss current prognostic and predictive factors with particular emphasis on those of relevance in routine histopathology, especially with respect to their clinical applications.

Adult↗
PubMed2001

Preoperative assessment of prognostic factors in breast cancer.

The adoption of preoperative diagnostic strategies involving fine needle aspiration cytology (FNAC) or core biopsy is well established, allowing the planning of operating lists and bed occupancy and patient involvement in therapeutic management. In addition to diagnosis, however, pathologists are increasingly being asked to provide pathological prognostic information from preoperative samples. This leader describes techniques for predicting prognosis and response to treatment on these specimens and some of the problems inherent in the determination of prognosis on small samples. For example, although histological grade can be assessed relatively reliably on either core or FNAC samples, the evaluation of tumour type (which includes an overall assessment of the architecture of a given tumour) may be less reliable on small preoperative samples. Other well recognised histological prognostic factors, such as vascular channel invasion or tumour size, cannot be determined accurately on small preoperative samples. For those patients who might benefit from neoadjuvant treatment, predicting the response to such treatments--for example, by the assessment of oestrogen receptor status--can readily be performed on either core biopsy or FNAC. In the future, other molecular markers such as C-erbB-2 might also prove beneficial in predicting response to newly developed treatments.

Biomarkers, Tumor↗
PubMed2001

Detecting which invasive cancers at mammographic screening saves lives?

OBJECTIVES: Assessment of the features of primary operable breast carcinomas arising in women known to subsequently develop metastatic disease, to show for which invasive breast cancers earlier detection by mammographic screening is potentially beneficial. These data were applied to a separate series of screen detected cancers. METHODS: Features associated with the development of metastatic disease after a previous operable breast cancer were ascertained from examination of histological sections of the initial primary carcinoma and in particular the incidence of nodal positivity and definite vascular invasion. Trends in the frequency of nodal involvement and vascular invasion according to histological grade, invasive size, and tumour type were then examined in a further group of 573 screen detected invasive cancers to predict the likelihood of development of systemic disease in these women. RESULTS: Of 173 women who developed metastatic disease after a previous operable breast cancer, 79 (72%) had nodal metastases and 62 (59%) had definite vascular invasion. A high proportion (84%) had either lymph node metastases or vascular invasion or both. The absence of vascular invasion and nodal involvement in invasive breast cancer indicated a low risk of subsequent development of metastatic disease. In the screen detected group, grade 1 invasive cancers <20 mm in size and grade 2 and 3 cancers <10 mm in size had low rates of nodal involvement and vascular invasion. There was a gradual trend to small size, lymph node negativity, and less vascular invasion when comparing screen detected ductal carcinoma of no special type, tubular mixed carcinoma, and tubular carcinoma. Cancers with a lobular component tended to be larger and more often lymph node positive than ductal and no specific type carcinomas. CONCLUSIONS: These data suggest that identification of grade 1 cancers less than 20 mm in size and grade 2 and 3 cancers less than 10 mm in size at screening is likely to be beneficial, with a lower likelihood of developing metastatic disease from these lesions. The detection of tubular mixed carcinomas and ductal carcinomas of no specific type also appears beneficial. However the detection of tumours with lobular features at breast screening does not seem to significantly benefit the patient.

Breast Neoplasms↗
PubMed2001

Screen detected ductal carcinoma in situ (DCIS): overdiagnosis or an obligate precursor of invasive disease?

OBJECTIVES: Ductal carcinoma in situ (DCIS) represents 20%-25% of malignancy detected at mammographic screening. This study aims to clarify the value of detecting DCIS at mammographic screening by assessing its biological characteristics and by comparing screen detected DCIS with a series of symptomatic DCIS lesions. METHODS: 222 Screen detected and 151 symptomatic cases of pure DCIS were identified. Their histological grade and the prevalence of necrosis were ascertained and compared. RESULTS: Of the screen detected lesions 28 (13%) were low grade, 40 (18%) intermediate grade, and 153 (69%) high grade. Of screen detected lesions 186 (87%) were necrotic and 29 (13%) were not. Of the 151 symptomatic lesions 24 (16%) were low grade, 34 (23%) intermediate grade, and 89 (61%) high grade. Of symptomatic lesions 112 (75%) were necrotic and 36 (24%) were not necrotic. Screen detected DCIS was more often necrotic (p=0.008) than symptomatic DCIS. CONCLUSIONS: As most DCIS detected at screening is high grade and necrotic, aggressive investigation of suspicious microcalcification at mammographic screening is advocated. Given the biological features of screen detected DCIS, the existence of an upper limit for the detection of DCIS by the NHS breast screening programme seems to be inappropriate.

Adult↗
PubMed2000

Breast cancer diagnosis using scattered X-rays.

Small-angle X-ray diffraction data has been collected from 99 ;core-cut' breast tissue specimens representing a number of different pathologies. Data in the range 75-1390 A have been compared with controls from patients with no breast disease. Bessel functions and Bragg maxima resulting from the fibrillar structure of collagen have been identified. The Bragg maxima indexed onto a 649 A lattice. Systematic differences in the intensities and D-spacings between the collagen of malignant, benign and normal tissue groups have been clearly demonstrated and quantified. These differences appear to be due to a significantly lower structural order within the malignant tissues. Possible explanations for this are discussed and the potential for utilizing this observation in cancer diagnosis is considered.

Journal Article↗
PubMed2000

Biological and clinical associations of c-jun activation in human breast cancer.

Sub-units and regulators of the activating protein-1(AP-1) complex have been implicated in breast-cancer biology, therapeutic response and prognosis. This study has immunocytochemically examined the impact of c-jun-protein activation on biological and clinical parameters in human primary breast cancers, employing an antibody specific for the serine 63-phosphorylated c-jun protein. Substantial nuclear immunostaining was commonly apparent, indicative of an activated c-jun pool, with associations with MAP-kinase-signalling elements, e.g., transforming growth factor-alpha (p = 0.04), epidermal growth factor receptor (p = 0.08), phosphorylated erk 1/2 MAP kinase (p = 0.001) and phosphorylated jun kinase (p = 0.05) Little association was noted with c-fos protein, perhaps indicating alternative AP-1 partners for c-jun with a diversity of cellular end-points. This may explain the lack of relationship with proliferation and grade, the imperfect association between increased c-jun activation and poorer survival (p = 0.061), and the apparent relationship with distant metastasis (p = 0.05). While increased c-jun activation related to poorer quality (p = 0.09) and shortened duration of endocrine response in oestrogen-receptor-positive patients (p = 0.018), no generalized effects on oestrogen-regulated gene products were noted, indicating that AP-1 influences on oestrogen-receptor/oestrogen-response element transactivation are unlikely to explain endocrine insensitivity. These data reinforce our belief that elevated AP-1 signalling influences aspects of the breast-cancer phenotype.

Breast Neoplasms↗
PubMed2000

A possible divergent role for the oestrogen receptor alpha and beta subtypes in clinical breast cancer.

We have examined the relative levels of oestrogen receptor beta (ERbeta) mRNA in 94 breast cancer specimens using a semi-quantitative RT-PCR procedure. We correlated its expression with ERalpha and various clinical, pathological and biochemical features of the disease. The level of ERbeta mRNA expression in these samples was found to be much lower than ERalpha. Although ERalpha mRNA species were found to be most frequently associated with histological grade I and II tumours, displaying tubular differentiation, low grades of nuclear pleomorphism and low mitotic activity, such features were not characteristic of ERbeta positive samples. Indeed, application of the Spearman rank correlation test revealed that there was an inverse association between ERbeta normalised levels and ERalpha protein HScore. Also ERbeta mRNA positive cancers were more frequently EGFR protein positive than their negative counterparts (p = 0.016), a feature normally associated with endocrine-insensitive disease. Our data suggest that although ERbeta levels are most likely lower than ERalpha, they may influence the biological behaviour of breast cancers containing low levels of ERalpha.

Breast Neoplasms↗
PubMed2000

Gamma linolenic acid with tamoxifen as primary therapy in breast cancer.

Gamma linolenic acid (GLA) has been proposed as a valuable new cancer therapy having selective anti-tumour properties with negligible systemic toxicity. Proposed mechanisms of action include modulation of steroid hormone receptors. We have investigated the effects of GLA with primary hormone therapy in an endocrine-sensitive cancer. Thirty-eight breast cancer patients (20 elderly Stage I-II, 14 locally advanced, 4 metastatic) took 8 capsules of oral GLA/day (total = 2.8 g) in addition to tamoxifen 20 mg od (T+GLA). Quality and duration of response were compared with matched controls receiving tamoxifen 20 mg od alone (n = 47). Serial tumour biopsies were taken to assess changes in oestrogen receptor (ER) and bcl-2 expression during treatment. GLA was well tolerated with no major side effects. T+GLA cases achieved a significantly faster clinical response (objective response vs. static disease) than tamoxifen controls, evident by 6 weeks on treatment (p = 0.010). There was significant reduction in ER expression in both treatment arms with T+GLA objective responders sustaining greater ER fall than tamoxifen counterparts (6-week biopsy p = 0.026; 6-month biopsy p = 0.019). We propose GLA as a useful adjunct to primary tamoxifen in endocrine-sensitive breast cancer. The effects of GLA on ER function and the apparent enhancement of tamoxifen-induced ER down-regulation by GLA require further investigation.

Administration, Oral↗
PubMed2000

Value of contralateral surveillance mammography for primary breast cancer follow-up.

Mammographic screening of the contralateral breast is often advocated during follow-up of women previously treated for primary operable breast cancer. The purpose of this study was to determine the value of this investigation. Between 1987 and 1995 a total of 5102 contralateral screening mammograms were performed biennially on 2511 women aged </= 70 years following treatment for primary operable breast cancer. Sixty-five metachronous contralateral breast cancers were identified: 21 (32%) at routine clinical examination, 24 (37%) at mammography, and 20 (31%) by patients between routine follow-up appointments. The prognostic features of metachronous cancers were better or similar to those of the first cancer in 59 of 65 (91%) cases. Because of the favorable prognostic characteristics of the contralateral cancer, mammographic screening may have contributed to the long-term survival of 16 of 26 women in whom the histologic characteristics of the first cancer predicted a good prognosis. The cancer detection rate with mammography for these women was 6.5 per 1000 contralateral mammogram investigations at a cost of pound3852 per cancer detected. The results of this study suggest that surveillance mammography of the contralateral breast is of value in women whose first cancer predicted a favorable prognosis.

Adult↗
PubMed2000

Molecular analysis of phyllodes tumors reveals distinct changes in the epithelial and stromal components.

Phyllodes tumors are fibroepithelial mammary lesions that tend to behave in a benign fashion but may undergo sarcomatous transformation. A study of clonality in these tumors has suggested that the epithelial component is polyclonal, but the stroma is monoclonal, and thus forms the neoplastic component of the lesion. In this study microsatellites on chromosome 1q and chromosome 3p were assessed for allelic imbalance (AI) in 47 phyllodes tumors; in all cases stroma and epithelium were analyzed separately. Ten of 42 (24%) phyllodes tumors showed AI at one or more markers on 3p, and 14 of 46 (30%) showed AI on chromosome 1. Five tumors had changes in both the epithelium and stroma. Eight tumors had changes only detectable in the stroma and eight, changes in the epithelium only. Three tumors exhibited low-level microsatellite instability in the epithelium but not in the stroma. The results show that AI on 3p and 1q does occur in phyllodes tumors and that it can occur in both the stroma and epithelium, sometimes as independent genetic events. These unexpected findings throw into doubt the classical view that phyllodes tumors are simply stromal neoplasms and raise questions about the nature of stromal and epithelial interactions in these tumors.

Alleles↗
PubMed2000

Loss of heterozygosity in bilateral breast cancer.

Women who develop bilateral breast cancer at an early age are likely to harbour germline mutations in breast cancer susceptibility genes. The aim of this study was to test for concordant genetic changes in left and right breast cancer of young women (age < 50) with bilateral breast cancer that may suggest an inherited breast cancer predisposition. Microsatellite markers were used to test for loss of heterozygosity (LOH) in left and right tumours for 31 women with premenopausal bilateral breast cancer. Markers adjacent to or within candidate genes on 17p (p53), 17q (BRCA1), 13q (BRCA2), 11q (Ataxia Telangiectasia-ATM) and 3p (FHIT) were chosen. Mutational testing for BRCA1 and BRCA2 was performed for cases where blood was available. Concordant LOH in both left and right tumours was demonstrated for at least one of the markers tested in 16/31(54%) cases. Where allelic loss was demonstrated for both left and right breast cancer, the same allele was lost on each occasion. This may suggest a common mutational event. Four cases showed concordant loss of alleles in both left and right breast cancer at D17S791 (BRCA1). BRCA1 mutations were identified in two of these cases where blood was available. Four cases showed concordant LOH at D13S155 (BRCA2). Concordant LOH was further demonstrated in seven cases for D11S1778 (ATM) and four cases for D3S1300 (which maps to the FHIT gene), suggesting a possible role for these tumour suppressor genes in this subgroup of breast cancer patients. No concordant allelic loss was demonstrated for D17S786 suggesting that germline mutations in p53 are unlikely in such cases of bilateral breast cancer.

Adult↗
PubMed2000

Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement.

In the histologic grading of invasive breast cancer with the Nottingham modification of the Scarff-Bloom-Richardson grading scheme (NSBR), it has been found that when pathologists disagree, they tend not to disagree by much. However, if tumor grade is to be used as an important parameter in making treatment decisions, then even this generally small degree of pathologist variability in assessing grade needs to be correlated with patient outcome. Findings from the Nottingham/Tenovus Primary Breast Cancer Study were used for patient outcome data. Kaplan-Meier survival curves were constructed for NSBR scores grouped according to the level at which pathologists tend to agree in assessing grade, from a reproducibility perspective. For example, if a given tumor were assessed by several pathologists as having either an NSBR score of 5 or 6, then what is the correct score--the intermediate-grade Score 6 assessments or the low-grade Score 5 assessments? By "regrouping" the Nottingham outcome data such that data from patients with Score 5 tumors are grouped with patients having Score 6 tumors (a 5-6 group), then the level in which the pathologists agreed with each other (that the tumor was either score 5 or 6) is better matched with patient outcome. In response to the above example, it was not surprising to find that patients with Score 5-6 tumors had a probability of survival between the established low and intermediate NSBR final combined grades. However, it is the discussion of this approach that highlights that optimal use of grading requires awareness of the level of pathologist agreement and understanding the value of pathologists' reaching consensus in assessments. Also, knowledge of possible clinical decision thresholds can help in providing relevant interpretations of grading results.

Adenocarcinoma↗
PubMed2000

Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases.

AIMS: This study presents a series of five cases in which metaplastic carcinoma, predominantly low-grade adenosquamous carcinoma, of the breast is seen arising within a background of a complex sclerosing lesion. This association has been recognized previously but has not been documented in detail. This study describes the characteristics of the components present in each case and discusses the existing literature. This observation adds further evidence to support an association between some types of invasive breast carcinoma and sclerosing lesions of the breast. METHODS AND RESULTS: Four of these cases were received as referral cases for opinion. The fifth was received as part of the routine surgical workload within our own institution. Two patients presented following mammographic screening and three symptomatically; their mean age was 62 years (range 49-68). The mean lesion size was 16 mm (range 7-24). All five lesions showed features of a complex sclerosing lesion/radial scar in the form of central sclerosis with elastosis and radiating benign entrapped tubules. One had associated benign papillary structures and two had focal benign squamous metaplasia. Four cases showed coexisting but distinct areas of low-grade adenosquamous carcinoma with glandular and squamous epithelial differentiation in a spindle cell background. One case had associated undifferentiated spindle cell carcinoma. Detailed immunophenotypic characteristics of two cases are presented. CONCLUSIONS: This series illustrates a postulated but previously unconfirmed association between an unusual form of metaplastic breast carcinoma (adenosquamous carcinoma) and complex sclerosing lesions. The mechanisms of induction of breast carcinoma are poorly understood but these observations further emphasize the potential for sclerosing lesion of the breast to be associated with, and possibly give rise to, invasive carcinoma of different types. The precise nature of the interaction between the pathological processes remains unclear.

Aged↗