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Biomedical subjects

I O Ellis

Publications and source records attributed to I O Ellis.

At least 127 records · Page 7Linked to original sources
PubMed1997

Early-onset breast cancer--histopathological and prognostic considerations.

Young age at diagnosis is claimed to be a prognostic factor in the natural history of breast cancer. Of 2879 patients aged < 70 years treated for primary operable breast cancer (< 5 cm diameter) at Nottingham City Hospital between 1973 and 1993, 120 were less than 35 years of age at diagnosis. Histopathological and prognostic variables were compared between patients aged < 35, 35-50 and 51-70 years. A significant reduction in metastasis disease-free survival and actuarial survival was seen in breast cancer patients aged < 35 years compared with the two older age groups. Patients aged < 35 years at diagnosis presented more frequently with high-grade cancers and vascular invasion. No differences were seen for tumour size or lymph node stage. The Nottingham Prognostic Index (NPI) was used to stratify cancers in each age group. Because of the tendency to high grade, a greater percentage of patients aged < 35 years fell into the poor-prognosis group. Within each prognostic group, no difference in actuarial survival was seen between age groups. The association of young age at diagnosis with a worse prognosis in this series is explained by a higher proportion of poorly differentiated cancers; age itself had no influence on the prognosis of the individual.

Adult↗
PubMed1997

Laminin and collagen IV subunit distribution in normal and neoplastic tissues of colorectum and breast.

To invade and metastasize, carcinomas must penetrate or lose their epithelial basement membrane (EBM), and then penetrate basement membranes (BMs) surrounding blood vessels, lymphatics, nerves and muscle cells. Knowledge of the composition of different BMs is necessary, so that appropriate antibodies and DNA probes are used to analyse these events. Laminin and type IV collagen are the principal BM components. However, recent studies show these two proteins exist in various isoforms, each of which is a heterotrimer of different subunit polypeptides. In this study, we analysed the distribution of laminin subunits, alpha 1 (lam), alpha 2 (lam), beta 1(lam), beta 2(lam) and gamma 1 (lam), and collagen IV subunits, alpha 1(IV), alpha 3(IV), alpha 4(IV) and alpha 5 (IV), in normal and neoplastic tissues of colorectum and breast. Subunits alpha 1(IV), alpha 1(lam), beta 1(lam) and gamma 1(lam) were detected in all BMs, while the distribution of alpha 3(IV), alpha 4(IV), alpha 5(IV) and alpha 2(lam) was much more restricted. In carcinomas, EBM staining for all subunits was invariably discontinuous or absent, consistent with the presence of complete EBM breaks. Use of antibody to alpha 1(lam) selectively stained the EBMs of carcinomas. Strong vascular staining for alpha 1(lam), beta 1(lam), gamma 1(lam) and alpha 1(IV) suggests an abundance of BM proteins in vessel walls, which may aid tumour cell attachment before vascular invasion. Within carcinomas, vascular BM staining for beta 2(lam) was clearly weaker than in normal tissues, which may reflect incomplete maturation of these vessels.

Adenoma↗
PubMed1997

The detection of ductal carcinoma in situ at mammographic screening enables the diagnosis of small, grade 3 invasive tumours.

This study was carried out to assess the frequency of ductal carcinoma in situ (DCIS) occurring within and surrounding grade 3 invasive tumours and the effect of its detection on size and nodal stage of invasive carcinomas at mammographic detection. Grade 3 tumours with either no associated DCIS or DCIS only within the invasive component were significantly larger in size than tumours with surrounding DCIS (P < 0.02) and were less likely to be under or equal to 10 mm in size (0% or 13% vs 30% respectively, P < 0.02). Tumours with mammographic calcification were more likely to be less than or equal to 10 mm in size than non-calcific tumours (32% vs 11% respectively, P < 0.05). This was because of the high frequency of tumours less than or equal to 10 mm in size in the linear/branching calcification group. Tumours showing calcification without a mass also appear to be a group with good prognostic features, with a mean size of 13 mm, 33% being 10 mm or less in size and only 17% being node positive. We have found that the presence of surrounding DCIS enables earlier detection of grade 3 invasive carcinomas because of the presence of mammographically visible calcification. Detection of calcification suggestive of DCIS should remain an important part of mammographic screening.

Breast Neoplasms↗
PubMed1997

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates.

In an attempt to improve the quality of the breast FNA specimens we instigated a continuing audit of this procedure in this hospital. All FNAs since 1990 have had the following recorded: mode of aspiration, e.g. freehand or image guided, patient presentation (screening or symptomatic), patient diagnostic category, cytological diagnosis and final histological diagnosis. Aspirator performance was assessed by means of the inadequate aspiration rate (IR) of FNAs performed on patients with a final diagnosis of cancer (FDC) and diagnostic category A patients (clinically or radiologically malignant lesions). An ongoing annual review of the performance of all the aspirators was undertaken, all of whom received individual feedback. Counselling and further training were offered where indicated by poor performance. Over the period 1990-1995 a total of 13537 FNAs were performed by 27 aspirators. The IR on category A and FDC cases over this period was 16.0% and 18.1%. The best performance achieved by an aspirator in a calendar year was an IR of 3.6% with no inadequate specimens in either FDC or category A lesions, and the best performance over the entire period was an average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases from 12.2% to 21.7%. There was a significant improvement in individual junior aspirator performance when their first year was compared with their last year on the unit. In some cases a deterioration in intra-aspirator performance was observed, from an IR of 6% to 33%. The overall IR rate of the unit remained stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared to be largely due to a high proportion of the aspirations being performed by experienced personnel with consistent IRs. However, concealed within the overall rate there were some poor performers who benefited from counselling and/or further training. These results indicate an important role for audit in identifying poor aspirators who benefit from targeted training and advice, thereby improving the quality of FNA specimens, and ultimately patient care.

Biopsy, Needle↗
PubMed1997

Use of reverse transcription-polymerase chain reaction methodology to detect estrogen-regulated gene expression in small breast cancer specimens.

We describe the development and use of a sensitive reverse transcription-PCR (RT-PCR) procedure to detect novel estrogen-regulated gene expression in small clinical breast cancer samples, in which such study would be extremely difficult by any other molecular or immunocytochemical means. Assay optimization for pLIV1, estrogen receptors (ERs), progesterone receptors, and pS2 gene products was carried out on 50 primary breast cancers for which comparative Northern analysis and immunocytochemical data were available. Using 27 amplification cycles and a 0.5 microM primer concentration, varying expressions of the gene products were recorded simultaneously with a constant densitometric signal for a coamplified endogenous control gene (alpha-actin). Good concordances were subsequently observed between pLIV1 status generated by RT-PCR and both Northern analysis (P = 0.002) and ER status by immunocytochemistry (P = 0.0244). Agreement was also noted between ER (P = 0.002), progesterone receptor (P = 0.0005), and pS2 (P = 0. 0023) RT-PCR and immunocytochemical methodologies. The RT-PCR assays were then applied to 10 needle core trucut biopsies in which similar relationships were obtained. Our results justify the future use of this RT-PCR methodology to examine new estrogen-regulated genes in small breast cancer samples, and it is envisaged that this technology will prove invaluable in many future breast cancer studies.

Biomarkers, Tumor↗
PubMed1996

High levels of allele loss at the FHIT and ATM genes in non-comedo ductal carcinoma in situ and grade I tubular invasive breast cancers.

Fifty-four grade 1 tubular breast cancers and nine non-comedo ductal carcinoma in situ samples have been analyzed for loss of heterozygosity using a series of microsatellite markers. Markers mapping to regions of the genome for which loss of heterozygosity has been documented previously in higher-grade breast cancers were selected for this analysis. Even within this group of good prognostic early breast cancers, genetic events are very common. The highest levels of loss were observed for D3S1300, which maps within an intron of the recently identified FHIT gene. High levels of loss were also observed within the ATM gene. These findings indicate that allele loss at FHIT and ATM may be an important early event in the development of sporadic breast cancer.

Acid Anhydride Hydrolases↗
PubMed1996

Prognostic significance of serum c-erbB-2 protein in breast cancer patients.

The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor prognosis in a number of studies. More recently it has also been suggested that c-erbB-2 expression may predict response to systemic therapy in patients with advanced breast cancer. The measurement of c-erbB-2 protein in the serum of breast cancer patients has now been reported, but the significance of this finding is not clear. In this study an ELISA assay was used to measure c-erbB-2 in the sera of 23 normal controls, 46 benign breast disease patients, and 119 breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in 13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46) of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage IV patients. The tissue expression of the c-erbB-2 protein showed no association with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and IV patients who had assessable disease the presence of the c-erbB-2 protein in the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum detection of the c-erbB-2 protein in Stage I/II patients predicted for a worsening of both survival outcome (p = 0.002) and disease free interval (p = 0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and Stage IV patients, although the latter did not reach statistical significance (p = 0.27). This study found that the presence of c-erbB-2 in the serum of breast cancer patients was of prognostic significance for all stages of disease.

Biomarkers, Tumor↗
PubMed1996

The impact of core-biopsy on pre-operative diagnosis rate of screen detected breast cancers.

The UK breast screening Surgical Quality Assurance guidelines suggest a target for pre-operative diagnosis of screen detected cancer of over 70%. Core biopsy was introduced in our breast screening assessment clinics in April 1994 and this study reports the impact of introducing core biopsy on the pre-operative diagnosis rate. Between April 1994 and March 1995, 100 cancers were detected. Results of fine needle aspiration cytology and core biopsies were studied to assess the contribution of each to the pre-operative diagnosis rate of cancer and comparison made with results from the previous 2 years. After introducing core biopsy pre-operative diagnosis rates rose from 72% to 90% (P < 0.0002) leading to a 64% reduction in diagnostic biopsies for screen detected cancer. Malignant results were obtained in 61% of first FNA (similar to previous years) and 74% of first core biopsies (combined 87%). Repeat FNA/core diagnosed three further cancers increasing the final pre-operative diagnosis rate to 90%. Final pathological examination after surgical excision demonstrated an increase in the preoperative detection of DCIS from 39% to 82% (P < 0.01) and invasive disease from 80% to 92% (P < 0.02). The introduction of core biopsy has significantly improved our management of screen detected breast cancer.

Biopsy, Needle↗
PubMed1996

Pure mucinous breast cancer-mammographic and ultrasound findings.

UNLABELLED: Aim to describe the mammographic and ultrasonographic features of pure mucinous breast cancer. PATIENTS AND METHODS: The mammographic features of 15 patients and ultrasonographic features of seven patients with pure mucinous breast cancer were reviewed retrospectively by three experienced breast radiologists. RESULTS: The commonest mammographic appearance was of a poorly defined (86%) lobulated (71%) mass which could contain calcification (14%). A well defined mass (14%) and suspicious calcifications without a mass (7%) were also seen. Ultrasound showed a mass lesion in all seven cases which was either hypoechoic (86%) or mixed echogenicity (14%); 86% had a heterogeneous internal echo pattern; 71% showed distal enhancement while none showed distal attenuation. CONCLUSION: The imaging features of pure mucinous cancer are different from more common types of breast carcinoma. It is possible to misinterpret the appearances of this slow growing tumour as a benign lesion due to rarity of speculation on mammography and distal attenuation on ultrasonography. Most cases do, however, show other features suggesting malignancy.

Adenocarcinoma, Mucinous↗
PubMed1996

Is ipsilateral mammography worthwhile in Paget's disease of the breast?

AIMS: To identify the clinical value of pre-operative ipsilateral mammography in patients with Paget's disease of the breast. METHOD: The mammograms and histological data of 27 patients with Paget's disease and 60 patients with symptomatic DCIS without Paget's disease were reviewed and compared. RESULTS: Forty-four percent of patients with Paget's disease had normal mammograms. Mammography did not discriminate between DCIS and invasive disease, and could not predict DCIS sub-type. DCIS was large cell in 80% of patients with Paget's disease. Given that large cell DCIS in non Paget's patients is normally visible mammographically, the large proportion of Paget's patients with normal mammography is difficult to explain, but could be due to the small size of the lesions. Comparison of the Paget's and non-Paget's groups showed that large cell solid disease was more common, small cell cribriform less common and normal mammography more common in the Paget's group. Given that mastectomy is the treatment of choice, the only clinical value of ipsilateral mammography in our unit would be to allow image guided core biopsy of any detected mammographic abnormalities to determine the presence of invasive disease prior to surgery, thus indicating the need for node sampling pre-operatively rather than as a delayed procedure. This study also confirms that mammography is of little help in deciding if breast conserving surgery is appropriate for individual cases of Paget's disease of the nipple due to the insensitivity of mammography in showing the site of disease.

Adult↗
PubMed1996

The positive predictive value of mammographic signs: a review of 425 non-palpable breast lesions.

The sensitivity of mammography in cancer detection needs to be high but is also important to achieve a high diagnostic specificity to avoid the morbidity associated with unnecessary surgical biopsy. We have reviewed the mammographic features of non-palpable breast lesions to identify factors which may improve the specificity of mammographic interpretation and reduce the number of open surgical biopsies for benign lesions. Four hundred and twenty-five surgical biopsies of non-palpable breast lesions were performed following image-guided localization between January 1987 and April 1994. The mammographic features of these lesions were reviewed and correlated with their histology. Two hundred and twenty-five of the excised lesions were malignant and 200 were benign giving a benign to malignant ratio of 0.88:1 and a positive predictive value (PPV) for malignancy of 53%. Pre-operative fine needle aspiration cytology was performed in 359 cases (84%). The PPV for the various mammographic abnormalities following the assessment process ranged from 4% for well defined masses to 94% for spiculate masses. The PPV for all microcalcifications was 45%. For impalpable lesions it is our policy to recommend surgical excision of all spiculate masses, parenchymal deformities and high risk microcalcifications. Ill defined masses are managed according to fine needle aspiration cytology (FNAC) and/or core biopsy results. Masses which are entirely well-defined are regarded as benign and are not recalled for assessment unless they are new or enlarging. Needle core biopsy has been added to our preoperative assessment of mammographically indeterminate microcalcifications with the aim of reducing the number of benign surgical biopsies.

Adult↗
PubMed1996

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators.

A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice.

Adult↗
PubMed1996

United Kingdom national audit of breast fine needle aspiration cytology in 1990-91--organization and level of activity.

A survey amongst members of the British Society for Clinical Cytology (BSCC) was performed in 1990 and 1991 into their experience of fine needle aspiration (FNA) cytology of the breast. Here we present the findings of that part of the survey covering organizational aspects of the service and methods of specimen handling. The replies demonstrate differences in approach to many of the topics covered. There is a preference for the examination of direct smears (rather than cytospins) with air dried Giemsa staining and wet fixation Papanicolaou staining finding nearly equal favour. Some perceived problems were highlighted, including availability and funding of training and quality assurance as well as facilities for liaison between pathologists, clinicians and radiologists.

Biopsy, Needle↗
PubMed1996

UK national audit of breast fine needle aspiration cytology in 1990-91: diagnostic criteria.

A survey into the practice of fine needle aspiration cytology of the breast amongst members of the British Society for Clinical Cytology in 1990 and 1991 was performed. This paper presents their reported use of diagnostic categories in reporting and the criteria found useful in the diagnosis of benign and malignant disease. A wide variety of diagnostic categories are in use. The criteria used in diagnosis largely follow recommendations found in standard textbooks, but some less well recognized features were also suggested.

Biopsy, Needle↗
PubMed1996

Screening interval breast cancers: mammographic features and prognosis factors.

PURPOSE: To review the mammographic features of screening interval breast cancers and to compare the tumor size, histologic grade, and lymph node involvement with those in screening-detected and unscreened symptomatic cancers. MATERIALS AND METHODS: Screening mammography was performed in 72,773 women aged 50-64 years. Ninety interval cancers were identified in 89 women. The mammographic and histopathologic features of these cancers were analyzed. RESULTS: At review of the screening mammograms, interval cancers were classified into four groups: 51 true-positive, 20 false-negative, seven mammographically occult, and 12 unclassified. The most common missed abnormality in the false-negative cases was architectural distortion. Interval cancers were larger, of higher grade, and more likely to have lymph node involvement than screening-detected tumors and were of similar size, histologic grade, and stage of lymph node involvement as symptomatic tumors. CONCLUSION: Prognosis in interval cancers is similar to that in symptomatic, unscreened tumors and statistically significantly worse than that in screening-detected cancers.

Breast Neoplasms↗
PubMed1996

Use of immunocytochemistry in the diagnosis of metastatic carcinoma.

Metastasis of unknown primary site is a common clinical problem. Immunohistochemistry has been shown to be a useful tool in the identification of the primary site. The availability of new antibodies specific for a wide range of antigens and working on routinely fixed, paraffin-imbedded material will ensure that this technique will continue to offer useful information in the search for an elusive primary tumour.

Diagnosis, Differential↗