Biomedical subjects

I O Ellis

Publications and source records attributed to I O Ellis.

At least 163 records · Page 9Linked to original sources

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

The expression of alpha B-crystallin in epithelial tumours: a useful tumour marker?

Alpha B-crystallin is a lens protein showing homology with small heat-shock proteins. We have previously demonstrated its expression in non-lenticular normal and diseased human tissues by immunostaining with a polyclonal antibody. In view of the expression seen in normal renal tubular epithelium, we have assessed the immunoreactivity of a variety of epithelial tumours, to determine the usefulness of alpha B-crystallin as a specific renal tumour marker. Carcinomas arising from tissues which normally express alpha B-crystallin, such as colo-rectal and thyroid carcinomas, showed a varying pattern and degree of immunoreactivity. The most consistently positive tumours, however, with typically strong cytoplasmic and cell membrane staining, were renal cell carcinomas, 90 per cent of which showed positive immunoreactivity. This pattern of staining, while not absolutely specific, is a useful aid to the diagnosis of renal carcinoma. When a metastic deposit or a small biopsy is being assessed, anti-alpha B-crystallin may be included in a panel of antibodies, the pattern of staining of which may direct the search for the primary site of the tumour.

Biomarkers, Tumor↗

PubMed1994

Epidermal growth factor receptor expression in breast cancer: association with response to endocrine therapy.

106 previously untreated breast cancer patients have been immunohistochemically analysed for EGF-R, ER, Ki67, and c-erbB-2 product. All patients received assessable endocrine therapy following disease progression. Significant associations were observed between EGF-R and ER (inverse) and Ki67 (direct). No association was observed between EGF-R and the c-erbB-2 product. EGF-R expression was significantly associated with the loss of endocrine sensitivity in breast cancer. This was observed in both ER positive and negative disease. In ER positive breast cancers, EGF-R expression had no significant influence on the quality of tumour remissions. Further sub-classification of the ER/EGF-R data by Ki67 immunostaining showed that in ER+/EGF-R-disease, increasing proportions of Ki67 positive cells were associated with a decline in the numbers of women experiencing good quality tumour remissions. A similar trend was also observed in ER+/EGF-R+ tumours. The presence of c-erbB-2 protein product did not influence endocrine sensitivity in any of the ER/EGF-R sub-groups.

Biomarkers, Tumor↗

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

Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology.

During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35-40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment-related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity.

Aged↗

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

The radiological appearances of invasive cribriform carcinoma of the breast. Nottingham Breast Team.

Invasive cribriform carcinoma (ICC) of the breast is characterized by a cribriform histological architecture. It is rare, accounting for 0.6% of breast cancers in Nottingham and has an excellent prognosis. Its radiological features have not been previously described. Preoperative mammograms were available in eight cases (6 symptomatic, 2 screen-detected) and preoperative ultrasound examinations in four. The tumour was mammographically occult in four (50%) cases. The four tumours which were visible on mammography all showed as a large (20-35 mm) spiculated mass and two contained a few flecks of punctate calcification. The ultrasound appearances were not entirely typical of breast carcinoma. Three of four showed an ill-defined, inhomogeneous solid mass, but without the distal acoustic attenuation found in 60-97% of other forms of breast carcinoma. We conclude that ICC has imaging characteristics distinct from tubular carcinoma, which is its closest histological analogue.

Adenocarcinoma↗

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↗

PubMed1994

Screening-detected and symptomatic ductal carcinoma in situ: mammographic features with pathologic correlation.

PURPOSE: To compare the mammographic and pathologic features of screening-detected and symptomatic ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The mammographic and pathologic features of 54 screening-detected and 77 symptomatic cases of DCIS were compared. Patients were aged 30-76 years (mean, 58 years). RESULTS: Diffuse involvement was seen in 10 patients (13%) with symptoms but in none of the screening-detected group (P < .05). The disease was radiologically more extensive in the symptomatic group. Calcifications in the symptomatic group (n = 48) were less likely to have a ductal distribution than those in the screening-detected group (n = 48) (30 [63%] vs 40 [83%], respectively; P < .05). At histologic examination in some cases, the symptomatic group (n = 76) included eight (11%) patients with cribriform-micropapillary, large-cell tumors (P < .05) and less comedocarcinoma (20 [26%] vs 23 [45%], respectively; P < .05) compared with the screening-detected group (n = 51). CONCLUSION: The results show differences in the radiologic and pathologic features of screening-detected and symptomatic DCIS.

Adult↗

PubMed1994

Interlaboratory comparison of DNA image analysis. Management group report of internal quality assurance programme in the CAAC breast cancer project.

The Clinically Applied Analytical Cytometry (CAAC) project was a concerted action project in a working group measuring DNA in breast cancer. An internal quality assurance programme was established on a voluntary basis to determine the level of concordance of DNA measurements between participating laboratories. Three rounds were achieved within the time scale of the project. For each round three slides (2 prepared with Feulgen, one unstained for "in house" preparation) bearing a population of human liver cells were sent to participating laboratories. The institutions were asked to measure 200 diploid, 100 tetraploid and 50 octaploid cells by means of the image cytometry system present in the laboratory. In the third round tumor cells were added. The features integrated optical density (IOD) and AREA were reported. In the three rounds the number of participating laboratories was 11, 14 and 11, respectively. The interlaboratory variation expressed as the CV of IOD for the three rounds ranged from 2-18%. Calculation of the 4c/2c and 8c/2c ratios revealed a high precision for most of the instruments. Comparison of measurements in specimens stained in the participating and central laboratory showed similar CV values. Measuring 200 nuclei in image analysis is too low a number to obtain a reliable estimate of the S-phase fraction. In conclusion, the interlaboratory intercomparison of DNA measurements performed on different instruments is well feasible and could facilitate improvement in quality standards.

Analysis of Variance↗

PubMed1994

Ideas in pathology. Ductal carcinoma in situ of the breast: a proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression.

UNLABELLED: The diagnosis of ductal carcinoma in situ of the breast (DCIS) has become common with the advent of breast screening programs. METHODS: Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumors were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis and morphology. This new classification defines three distinct tumor groups: pure comedo in 19 (25.0%) cases, DCIS with necrosis (non-pure comedo) in 21 (27.6%) patients, and DCIS without necrosis in 36 (47.4%) of cases, the latter group comprising largely classical cribriform or micropapillary architectural subtypes. RESULTS: Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (P < 0.01 [anova]). A preliminary analysis of disease recurrence and disease-free survival in a large series of 391 cases of pure DCIS showed that of 181 cases of pure comedo DCIS there were 19 local recurrences at the 7-year stage (82% 7-year disease-free survival), with 5 local recurrences in 51 cases of DCIS with necrosis (non-pure comedo) (85% 7-year disease-free survival) and only 6 local recurrences in the 159 cases of the DCIS-without-necrosis subgroup (94% 7-year disease-free survival). The chi 2 value for the frequency of disease recurrence of all cases of DCIS with necrosis (i.e., combining the groups of comedo DCIS and DCIS with necrosis (non-pure comedo)) as compared to DCIS without histological evidence of necrosis was 5705 (df = 2; P = 0.0001), and the chi 2 for disease-free survival of types of DCIS with necrosis as compared to cases without necrosis was 178 (df = 2; P = 0.0001). This analysis indicates that the histological presence of necrosis appears to be a relatively powerful predictor of increased disease recurrence and poorer disease-free survival after treatment for DCIS. CONCLUSIONS: Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of more biologically aggressive in situ breast cancer with an intermediate proliferative fraction as compared with the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi 2 analysis. Further larger studies are required to establish if DCIS with necrosis (non-pure comedo) also shows a greater tendency to local recurrence after breast conservation treatment than do subtypes of DCIS without necrosis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in situ mammary carcinoma.

Biomarkers, Tumor↗

PubMed1993

Use of tumour marker immunoreactivity to identify primary site of metastatic cancer.

OBJECTIVES: To determine whether variations in the expression of tumour related antigens can predict the origin of tumours. DESIGN: Immunohistological study of tumour marker expression in primary adenocarcinomas and respective metastatic deposits. Antibodies to the following tumour markers were used: polymorphic epithelial mucin (NCRC-11 and SM3), carcinoembryonic antigen, carcinoembryonic antigen with non-specific antigen co-specificity, CA125, CA19.9, prostate specific antigens, and thyroglobulin. SETTING: Histopathology department of teaching hospital. SUBJECTS: 100 pathology sections of metastatic adenocarcinoma and their related primary tumours. MAIN OUTCOME MEASURES: Concordance of reactivity between primary and metastatic tumours. Reactivity profiles of tumour sites. RESULTS: The correct primary site of origin was predicted in 70% (33/47) of tumours in men and 54% (27/43) tumours in women with antibodies SM3, 288, CA19.9, CA125, and PSA (men only). Specificities ranged from 68% for breast tumour to 98% for prostate tumour. CONCLUSION: Use of tumour markers in patients presenting with metastatic adenocarcinoma of unknown origin can help localise the probable primary sites and reduce the need for extensive and expensive imaging techniques.

Adenocarcinoma↗

PubMed1993

Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast.

Metallothioneins (MTs) are ubiquitous low-molecular-weight proteins with a high affinity for heavy metal ions such as zinc, copper and cadmium. MT over-expression has been associated with resistance against anticancer drugs. In the present study we investigated 86 cases (45 cases of tumour category pT1 and 41 of category pT2) of routinely fixed and paraffin-embedded primary breast carcinomas immunohistochemically with a monoclonal antibody to an epitope of MT shared by its I and II isoforms. Immunohistochemically demonstrated MT over-expression was found in the invasive components of 7 of 32 pT1 and 17 of 28 pT2 invasive ductal carcinomas, whereas all 26 invasive lobular carcinomas gave weak or negative results. Fourteen of 17 pT2 and 2 of 7 pT1 invasive ductal carcinomas with MT over-expression developed metastases during follow-up with poor prognostic outcome. In contrast only 3 of 11 pT2 and none of the 25 pT1 cases without MT over-expression had a poor clinical course (P < 0.001). It is concluded that MT over-expression is associated with significantly poor prognosis particularly in pT2 invasive ductal breast carcinomas.

Adult↗

PubMed1993

p53 protein expression in mammary ductal carcinoma in situ: relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein.

The immunohistochemical expression of the p53 gene protein was examined in a consecutive series of 143 cases of pure ductal carcinoma in situ (DCIS) of the breast. Expression of wild-type and/or mutant p53 protein was detected in 36 (25.2%) of the cases examined, as evidenced by positive nuclear staining with the monoclonal antibody DO 7. Thirty-four (35.8%) of the large cell cases showed p53 protein expression compared with two (4.1%) of the small cell cases (chi 2 = 15.3 [df = 1], P < .001). p53 Protein expression also was associated with an increased histologic degree of necrosis, with a nearly significant association of negative tumor estrogen receptor status and p53 protein expression. No significant association of p53 protein expression and c-erbB-2 protein expression was seen. Immunohistochemical expression of p53 protein is present in approximately 25% of DCIS cases and is confined almost exclusively to large cell DCIS, a morphologic subtype of in situ breast carcinoma thought to be more biologically aggressive. Expression of p53 protein may be important in the neoplastic progression of DCIS, reflecting the acquisition of p53 gene mutations in large cell DCIS cases. Therefore, p53 may be implicated in mammary tumor evolution from in situ to invasive disease.

Biomarkers, Tumor↗

PubMed1993

Relationship between EGF-R, c-erbB-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity.

The expression of the epidermal growth factor receptor (EGF-R), c-erbB-2 protein product and Ki67 have been evaluated in 105 breast cancers of known responsiveness to endocrine therapy using immunohistochemistry. EGF-R staining was observed in 62 of the tumours and was significantly associated with elevated rates of cell proliferation (%Ki67 positive cells) and loss of hormone sensitivity. In contrast, c-erbB-2 expression was not correlated with cell proliferation rates and was less strongly related to hormone insensitivity. Subdivision of the EGF-R data according to c-erbB-2 measurements revealed an association between c-erbB-2 immunostaining and worsened patient outlook and hormone insensitivity in moderately EGF-R-positive tumours. c-erbB-2 immunostaining in highly EGF-R-positive tumours did not further contribute to the already poor prognosis of these patients. These data confirm the prognostic importance of EGF-R measurements in breast cancer and may infer a functional interaction between this protein and the c-erbB-2 protein product in the aberrant growth of a subset of breast tumours.

Breast Neoplasms↗