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E A Mallon

Publications and source records attributed to E A Mallon.

18 recordsLinked to original sources
PubMed2005

IHC for Her2 with CBE356 antibody is a more accurate predictor of Her2 gene amplification by FISH than HercepTest in breast carcinoma.

BACKGROUND: Her2 (c-erbB-2/neu) overexpression in breast carcinoma predicts response to the anti-Her2 monoclonal antibody, trastuzumab, and is associated with a poor prognosis. When considering patients for trastuzumab treatment, Her2 protein expression is measured by imunohistochemistry (IHC) and, where staining is equivocal, by fluorescence in situ hybridisation (FISH) detection of Her2 gene amplification. AIMS: To compare IHC using CBE356 with IHC using the Food and Drug Administration approved HercepTesttrade mark. METHODS: CBE356 and HercepTest were analysed using 167 FISH characterised breast carcinomas. Immunohistochemical expression of Her2 was measured semiquantitatively. Sensitivity, specificity, predictive values, and overall accuracy were calculated for both IHC methods using gene amplification by FISH as the end point, and IHC and FISH assays were tested in Kaplan-Meier survival analysis. RESULTS: The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CBE356 positive (2+ and 3+) cases were 94%, 89%, 95%, 84%, and 97%, respectively, and of HercepTest positive (2+ and 3+) cases were 91%, 66%, 98%, 92%, and 91%, respectively. A positive result with CBE356, HercepTest, or FISH was associated with significantly decreased overall survival (log rank p = 0.005, p = 0.0017, and p = 0.0005, respectively). CONCLUSIONS: Positive IHC staining for Her2 using CBE356 is 3% more accurate and 23% more sensitive at predicting Her2 gene amplification by FISH than positive staining with HercepTest. Negative IHC using CBE356 antibody is 6% more likely to represent a truly negative result than negative staining with HercepTest. Overall, CBE356 was a more accurate predictor of Her2 gene amplification by FISH than HercepTest.

Adult↗
PubMed2002

Adjuvant ovarian ablation vs CMF chemotherapy in premenopausal breast cancer patients: trial update and impact of immunohistochemical assessment of ER status.

This trial, initiated in 1980, examined the relative values of adjuvant ovarian ablation and chemotherapy comprising cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in premenopausal women with pathological stage II breast cancer. With median follow-up for patients still alive of 13.9 years, there is no difference in survival between women receiving ovarian ablation and CMF (hazard ratio 1.01; 95% CI: 0.74, 1.37). Tumour oestrogen receptor (ER) status was assessed at the time using biochemical ligand-binding assay and retrospectively by immunohistochemistry (IHC). Agreement between these two methods was only fair, but both confirmed the importance of ER status in determining appropriate adjuvant systemic therapy. A statistically significant interaction between IHC quick score and treatment (P=0.001) showed ovarian ablation was more beneficial for patients with a positive quick score, whereas women with a quick score of 0 had a significantly higher risk of death with ovarian ablation (2.33; 95% CI: 1.30, 4.20). We have shown that IHC identifies women with ER 'poor' tumours for whom endocrine manipulation is not appropriate.

Journal Article↗
PubMed2001

Evaluating HER2 amplification and overexpression in breast cancer.

The development of Herceptin (Trazumatab) makes testing for HER2 status important for choosing optimal therapy in breast cancer. This study addresses the precision, accuracy, and reproducibility of HER2 assays. HER2 was assessed retrospectively by immunohistochemistry (IHC) with Dako 'Herceptest', by IHC with the monoclonal antibody CB11, and by fluorescence in situ hybridization (FISH, PathVysion), in a series of 216 formalin-fixed breast carcinomas including 191 for which quantitative HER2 data from radioimmunohistochemistry (Q-IHC) were available. All tests were scored independently by two observers. Positivity rates varied between Herceptest (12.6%), FISH (19.4%), and CB11 IHC (28.5%). Kappa values showed that IHC-based tests were more susceptible to inter-observer variation (kappa=0.67 and 0.74 for Herceptest and CB11, respectively) than FISH (kappa=0.973). Overall test accuracy (see the Materials and methods section) for CB11 IHC (83.8%) was lower than Herceptest (87.4%) or FISH (93.2%). FISH predicted p185 HER2 overexpression (determined by Q-IHC) better (concordance index C.Ind. 0.90) than CB11 IHC (C.Ind.=0.85) or Herceptest (C.Ind.=0.81). Of 42 cases with gene amplification by FISH, 67% were positive in the Herceptest (2+ or 3+) vs. 83% with CB11. Of 174 cases negative by FISH, 96% were negative in the Herceptest and 68% with CB11. In conclusion, FISH is the most accurate, reproducible, and precise predictor of HER2 overexpression in routine diagnostic laboratories.

Antibodies, Monoclonal↗
PubMed2001

What the clinician needs from the pathologist: evidence-based reporting in breast cancer.

Histopathology has a vital role in determining breast cancer management and pathologists must be part of the clinical team. Carcinoma size, grade, and especially lymph node status remain the best available prognostic factors. Metastatic carcinoma in axillary nodes is more important than any other prognostic factor presently available. ER status is an important predictor of response to endocrine manipulation, but its independent prognostic significance, and that of micrometastatic disease, circulating carcinoma cells and other molecular factors, even well-studied ones such as HER2 status, are less clear. Pathology is the first clinical speciality to subject its practice to rigorous scientific analysis, and it has stood up well. However, workers without appropriate experience in Pathology or scientific design have created difficulties by undertaking poorly planned studies with ill-defined end-points, lacking appropriate quality control. New analytical techniques and therapeutic targets make it essential that we learn from past mistakes and integrate pathologists into the research teams pursing clinical trials and the assessment of new bio-markers. Without this, input resource will be wasted on false leads that could have been curtailed. Morphology alone will not be enough to select patients likely to benefit in trials of new therapies, but selection 'tests' must be appropriate. The confusion of tests for selection of patients to receive Herceptin shows what happens when this process fails. Much of the microarray data being put into data-bases has no quality control, and meta-analysis of this data will produce even more conflict than the clinical trials. This can be avoided, as the ability to standardise is available.

Bone Marrow Neoplasms↗
PubMed2001

Ductal carcinoma in situ of the breast -- among factors predicting for recurrence, distance from the nipple is important.

AIMS: To assess local and systemic recurrence rates and factors predicting for recurrence in patients treated for ductal carcinoma of the breast (DCIS). METHODS: Patients with DCIS treated between January 1986 and January 1997 were identified. All pathology specimens were reviewed. DCIS type, lesion size, nuclear grade and margin clearance were assessed. Mammograms were reviewed and mammographic patterns, size, type of lesion and distance from the nipple were measured. Treatments and subsequent outcomes were established by case note review. Factors predicting for recurrence were analysed by both univariant and multivariant analysis. RESULTS: Of the 220 patients, 153 (70%) had breast-conserving surgery. Sixty-seven (30%) had a mastectomy. Ninety-seven patients had adjuvant therapy of which 22 had radiotherapy alone, 54 had tamoxifen alone and 21 had radiotherapy and tamoxifen. Following mastectomy, two patients developed axillary recurrences. Following breast-conserving surgery 20 (13%) patients developed local recurrences, of which one developed systemic disease and died from breast cancer. CONCLUSIONS: Mammographic nipple to lesion distance of <40 mm and high/intermediate nuclear grade were the only factors found to increase the likelihood of recurrence.

Adult↗
PubMed1999

Influence of tumour bed assessment on local recurrence following breast-conserving surgery for breast cancer.

AIMS: To assess the impact of adopting a policy of tumour bed assessment with selective re-excision in patients undergoing breast-conserving surgery for breast cancer. METHODS: Tumour bed assessment was introduced in our institution in 1988. Patients treated prior to 1988 (125 patients) were compared with patients treated post-1988 (239 patients) for clinico-pathological factors, surgical and adjuvant therapy. Outcome measures were examined at a fixed 5-year follow-up period for each patient. RESULTS: There were a greater number of small, node-negative, oestrogen receptor tumours post-1988, probably due to the influence of the National Breast Screening Programme. There was also a difference in the prescription of adjuvant systemic therapy between the two cohorts. The incidence of tumour bed positivity was 30.5%. The re-excision rate was 16.4%. There was a significant fall in the incidence of local recurrence from pre-1988 (15.7%) to post-1988 (2.5%). CONCLUSION: By adopting a policy of tumour bed assessment with selective re-excision, a low local recurrence rate has been achieved. The improvement in systemic recurrence and breast cancer-related death rate are mainly secondary to other factors.

Adult↗
PubMed1999

Margin assessment by cavity shaving after breast-conserving surgery: analysis and follow-up of 543 patients.

AIMS: To analyse cavity shaving as a method of assessing completeness of surgical excision after breast-conserving surgery. METHODS: Shavings were taken from the wall of the cavity remaining in the breast after breast-conserving surgery in 543 women. Each shaving was extensively sectioned and the presence and type of microscopic disease recorded. Disease in cavity shavings (tumour bed positivity) was correlated with clinicopathological factors as well as overall survival. RESULTS: Tumour bed positivity (TBP) was found in 37% of patients (16% with invasive disease). Patients were selected for further surgery according to the extent of positivity, which varied widely. A total of 15% of patients underwent re-excision or mastectomy. TBP was significantly associated with high tumour grade, presence of an extensive intraduct component, young age and large tumour diameter. It was also associated with a significantly shorter overall survival when compared to patients who were tumour bed negative. CONCLUSIONS: Cavity shaving is a practical and sensitive method of assessing completeness of excision after breast-conserving surgery. In addition it may provide useful prognostic information.

Adult↗
PubMed1995

Interphase cytogenetic analysis of erbB2 and topoII alpha co-amplification in invasive breast cancer and polysomy of chromosome 17 in ductal carcinoma in situ.

Breast cancer is a genetically complex disease. Fluorescence in situ hybridisation can be used to analyse the genetics of breast-cancer progression in interphase cytogenetics. We have analysed the histological distribution of erbB2 and topoll alpha co-amplification in paraffin sections of invasive breast cancer and show that the co-amplified loci share the same histological distribution in the tumour and have a similar nuclear distribution within individual nuclei. Regions of the tumours without amplification are easily recognized and tumours with erbB2 and topoll alpha co-amplification can be distinguished from those with erbB2 amplification alone. In addition, FISH was used to show polysomy of chromosome 17 in non-invasive ductal carcinoma in situ of the breast and erbB2 amplification in both the invasive and non-invasive components of a breast cancer biopsy. This report of an interphase cytogenetic analysis of non-invasive breast carcinoma in situ demonstrates the usefulness of FISH for the genetic study of breast cancer progression.

Aneuploidy↗
PubMed1994

Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE: To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN: Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING: Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS: 1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES: Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS: There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS: Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.

Aged↗
PubMed1993

Nasal leishmaniasis.

Leishmaniasis is an uncommon condition in Western Europe, except around the Mediterranean coast. However, it may occasionally be seen in the United Kingdom, in patients who acquired the infection in foreign lands. An unusual case of localized cutaneous leishmaniasis recidiva affecting the nose after septal surgery is presented.

Adult↗
PubMed1990

Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer.

In 31 patients with carcinoma of the breast the phenotype and activation status of tumour infiltrating lymphocytes (TILs) was analysed by flow cytometry. The predominant cells, in all patients, were T lymphocytes and in the majority of cases CD8+ (cytotoxic/suppressor) T lymphocytes were present in greater numbers than CD4+ (helper) T lymphocytes. There was no relationship between the degree of lymphocytic infiltration and either tumour stage or grade but there appeared to be an inverse correlation with the levels of oestrogen receptor (ER) in the tumour (P less than 0.01). Both populations of T cells had significantly higher numbers of cells carrying HLA DR (class II major histocompatibility antigen) than the equivalent populations in peripheral blood from the same patient group (P less than 0.001). The transferrin receptor was found on similar numbers of CD8+ T cells in peripheral blood and among the tumour infiltrating lymphocytes while more of the CD4+ T cells infiltrating the tumour were found to carry this receptor (P = 0.034). The Tac (CD 25) antigen was also on similar numbers of CD8+ T cells from both peripheral blood and the tumour but was on fewer of the CD4+ T cells in the tumour with respect to peripheral blood (P = 0.029). In both TILs and blood lymphocytes, the Tac antigen was consistently present on greater numbers of CD4+ T lymphocytes than on the CD8+ T lymphocytes (P less than 0.001) and as this is a component of the interleukin 2 (IL-2) receptor this may be of relevance to the use of IL-2 in TIL cancer therapy.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Semiquantitative analyses of fine needle aspirates from benign and malignant breast lesions.

A scoring system for the assessment of fine needle aspirates of benign and malignant breast lesions was devised which showed a positive correlation (r = 0.67) between the scores obtained from the fine needle aspirates from ductal carcinomas and the Bloom and Richardson-type scores for their paired excision biopsy specimens. This system permitted grades II and III ductal breast carcinoma to be distinguished reliably from grade I tumours but no correlation with the lymph node state of patients with breast carcinoma was shown. Some overlap between the scores for grade I ductal carcinomas and some benign lesions was found, and this underlines a need for caution in the reporting of such equivocal aspirates. No cytological features that distinguished reliably ductal from lobular carcinoma were identified but the same spectrum of severity of cytological abnormality in the ductal and lobular carcinoma aspirates was seen. This system may be of prognostic value in the assessment of lobular carcinoma which has hitherto defied histological grading.

Adenofibroma↗
PubMed1987

ANF (99-126) and its propeptide, ANF (1-16) are secreted simultaneously from the human atrial myocyte.

We have raised antisera to two synthetic peptides representing different portions of the human pro-atrial natriuretic factor (ANF) molecule; one antiserum identifies active human ANF, the 28-amino-acid sequence on the C-terminal end of the prohormone [ANF (99-126)], and the other detects ANF (1-16), the first 16-amino-acid sequence at the N-terminal end of the prohormone. With ultrastructural immunocytochemistry we have studied the distribution staining for both peptides within the myocytes in surgically excised human auricular appendages. Most of the endocrine granules stained with equal density for both ANF (1-16) and ANF (99-126). Also, double immuno-staining techniques on the same tissue section showed that both the C-terminal peptide and the N-terminal peptide co-existed within the same endocrine granules. It has been shown that, like other endocrine cells, atrial myocytes secrete their stored peptides by exocytosis of their granules. Therefore, our observations suggest that both the main active hormone, ANF (99-126), and the N-terminal propeptide ANF (1-16) are secreted simultaneously from the cell.

Atrial Natriuretic Factor↗
PubMed1986

Atrial natriuretic peptide in the heart and pancreas.

We used antisera to pure atrial natriuretic peptide to localise this peptide by immunocytochemistry in rat and human tissue. We showed that both rat and human atrial cardiocytes gave a positive reaction while ventricular cardiocytes were consistently negative. Peripheral islet cells in rat but not in human pancreas also showed positive staining for ANP. We showed by double labelling techniques that the ANP was present in the glucagon containing cells.

Animals↗