Biomedical subjects

Claire Paish

Publications and source records attributed to Claire Paish.

3 recordsLinked to original sources

PubMed2006

Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance.

BACKGROUND: Breast cancer is recognised to be a heterogeneous disease with a range of morphological appearances and behaviours. The recently recognised basal phenotype (BP) is associated with poor survival, but the clinical implications of this class of breast cancers remain to be adequately defined. METHODS: We have examined a well-characterised series of 1872 invasive breast carcinomas with a long term follow-up to assess the clinical significance of BP. RESULTS: A pragmatic definition of the BP as immunophenotypic evidence of basal cytokeratins CK5/6 and/or CK14 expression was used. These tumours were associated with shorter overall survival and disease-free interval in our series as a whole and in both the lymph node (LN) negative and LN positive subgroups. When stratified by histological grade, BP was of highly significant prognostic value in grade 3 but not in grades 1 or 2 tumours. Similarly, it was associated with poor survival in the moderate group of the Nottingham prognostic Index but not in the other groups. In a subgroup comprising LN negative grade 3 tumours, BP was the most powerful prognostic marker followed only by tumour size, while the other variables were non-significant. Patients with BP were more likely to respond to chemotherapy than those with non-basal tumours. CONCLUSIONS: Our results provide robust evidence that BP is an important class of breast cancers with a particularly aggressive behaviour in patients with LN negative grade 3 disease. We recommend routine identification of BP in breast cancer and the development of effective adjuvant treatment strategies. These are important observations as these tumours typically lack hormone receptor and HER-2 overexpression limiting the range of relevant adjuvant therapies.

Aged↗

PubMed2005

High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses.

Recent studies on gene molecular profiling using cDNA microarray in a relatively small series of breast cancer have identified biologically distinct groups with apparent clinical and prognostic relevance. The validation of such new taxonomies should be confirmed on larger series of cases prior to acceptance in clinical practice. The development of tissue microarray (TMA) technology provides methodology for high-throughput concomitant analyses of multiple proteins on large numbers of archival tumour samples. In our study, we have used immunohistochemistry techniques applied to TMA preparations of 1,076 cases of invasive breast cancer to study the combined protein expression profiles of a large panel of well-characterized commercially available biomarkers related to epithelial cell lineage, differentiation, hormone and growth factor receptors and gene products known to be altered in some forms of breast cancer. Using hierarchical clustering methodology, 5 groups with distinct patterns of protein expression were identified. A sixth group of only 4 cases was also identified but deemed too small for further detailed assessment. Further analysis of these clusters was performed using multiple layer perceptron (MLP)-artificial neural network (ANN) with a back propagation algorithm to identify key biomarkers driving the membership of each group. We have identified 2 large groups by their expression of luminal epithelial cell phenotypic characteristics, hormone receptors positivity, absence of basal epithelial phenotype characteristics and lack of c-erbB-2 protein overexpression. Two additional groups were characterized by high c-erbB-2 positivity and negative or weak hormone receptors expression but showed differences in MUC1 and E-cadherin expression. The final group was characterized by strong basal epithelial characteristics, p53 positivity, absent hormone receptors and weak to low luminal epithelial cytokeratin expression. In addition, we have identified significant differences between clusters identified in this series with respect to established prognostic factors including tumour grade, size and histologic tumour type as well as differences in patient outcomes. The different protein expression profiles identified in our study confirm the biologic heterogeneity of breast cancer and demonstrate the clinical relevance of classification in this manner. These observations could form the basis of revision of existing traditional classification systems for breast cancer.

Breast Neoplasms↗

PubMed2005

A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes.

Amplification of 8p11-12 is a well-known alteration in human breast cancers but the driving oncogene has not been identified. We have developed a high-resolution comparative genomic hybridization array covering 8p11-12 and analysed 33 primary breast tumors, 20 primary ovarian tumors and 27 breast cancer cell lines. Expression analysis of the genes in the region was carried out by using real-time quantitative PCR and/or oligo-microarray profiling. In all, 24% (8/33) of the breast tumors, 5% (1/20) of the ovary tumors and 15% (4/27) of the cell lines showed 8p11-12 amplification. We identified a 1 Mb segment of common amplification that excludes previously proposed candidate genes. Some of the amplified genes did not show overexpression, whereas for others, overexpression was not specifically attributable to amplification. The genes FLJ14299, C8orf2, BRF2 and RAB11FIP, map within the 8p11-12 minimal amplicon, two have a putative function consistent with an oncogenic role, these four genes showed a strong correlation between amplification and overexpression and are therefore the best candidate driver oncogenes at 8p12.

Breast Neoplasms↗