S R Lakhani

..To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients...

..This study evaluates the immunohistochemical profiles of tumors arising in patients with mutations in these genes...

..But how did the traditional methods of cancer diagnosis and prognosis develop, and how can high-throughput techniques contribute?..

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..Four polymorphisms were detected but no pathogenic mutations were identified. The results indicate that E-cadherin is unlikely to act as a susceptibility gene for LCIS...

..Our aim was to analyse a series of metaplastic breast carcinomas (MBCs) using this panel plus two other basal markers (CK14 and p63) and progesterone receptor (PR), to define how frequently MBCs show a basal-like immunophenotype...

..Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated...

..These alterations are also commonly seen in nonapocrine breast cancer. The data are consistent with apocrine hyperplasia as a putative nonobligate precursor of apocrine carcinoma...

..We also confirm and extend our original observation of loss of the wild-type BRCA1 allele in some clones, and loss of the mutant allele in others, demonstrating that loss of either allele is a stochastic event...

..Here we review the molecular characteristics of special types of breast cancer, with special emphasis on their microarray-based expression profiles and their impact on our understanding of breast cancer...

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..Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC...

..These results demonstrate a close association between BAG-1 and functional ER expression and suggest BAG-1 may be useful as a therapeutic target or prognostic marker in breast cancer...

..These data represent profiles of the transcriptional changes associated with ERBB2-related pathways in the breast, and identify novel and potentially useful targets for prognosis and therapy...

..These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma...

..The significance of AI in the pathogenesis of HUT or its subsequent progression to carcinoma is not yet clear and requires further investigation...

..Our aim was, therefore, to compare contrast enhanced magnetic resonance imaging (CE MRI) with mammography for screening...

..CGH has been instrumental in dissecting distinct molecular pathways toward breast malignancy and in establishing a direct relationship between genotype and clinical pathological features...

..Robust characterization of this basal group is necessary if it is to have a major impact on management of patients with breast cancer...

..This study brings into question the previously described profile of breast 'stem cells' based on CK5/6 staining and hence the breast cancer progression model and classification based on this phenotype...

..These data provide a framework for the interpretation of breast cancer molecular profiling experiments, the identification of potential new diagnostic markers, and development of novel indicators of prognosis...

..Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer...

..Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas...

..This analysis demonstrates the utility of 14-3-3sigma as a new adjunct antibody for characterization of myoepithelial cells and myoepithelial lesions and it may be a novel prognostic factor for breast cancer patients...

..However, little is known about the putative therapeutic targets for these tumors. The aim of this study was to characterize CLCs at the molecular genetic level and identify putative therapeutic targets...

..We review current knowledge and the contribution of molecular genetics in the understanding of breast cancer precursors and pre-invasive lesions...

..LCIS is now considered a risk factor and a non-obligate precursor for the subsequent development of invasive cancer...

..We investigated whether HER2 and EGFR overexpression was present and evaluated gene amplification in a series of metaplastic breast carcinomas...

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..This review presents our perspective on its broader biological significance and its potential use as a model system for understanding breast carcinogenesis...

..The other mutation detected in MLH1 was a TAC-->TAA substitution codon 750 (exon 19) creating a stop codon, predicted to generate a truncated protein. These findings suggest that mutations in MLH1 may underlie a subset of LCIS cases...

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..If IMF tissue is resected and the immediate breast reconstruction is performed, the superficial fascial system should be reconstructed after excision of the IMF tissue in order to recreate the inframammary crease...

..The limited data from these experiments do not reveal a specific predisposition locus...

..However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management...

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..We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer...

..Antibodies to the oestrogen receptor, progesterone receptor, p63, and c-kit (CD117) proved to be useful adjuncts to differentiate between these lesions...

..We have also demonstrated LOH using markers on chromosome 16q in 8/14 (57%) sporadic cylindromas, indicating that the cyld1 gene is likely to be involved in the genesis of both familial and sporadic cylindromas...

..This chapter provides an overview of the methods necessary to carry out the production of membrane-based cDNA arrays and the subsequent synthesis and hybridization of radiolabeled cDNA probes...

..Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases and poorer prognosis than other carcinomas...

..CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH)...

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..Although we identified many novel variants, we found no evidence that highly penetrant germline mutations in these five genes contribute to familial breast cancer susceptibility...

..We assessed the value of tumor immunohistochemical markers in conjunction with genetic and evolutionary approaches for investigating the clinical significance of unclassified variants...

..Misclassification of tumors may lead to mismanagement of patients in clinical practice, particularly in the context of in situ disease at margins...

..In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion...

..These immunohistochemical data, combined with genomic studies, may lead to better identification and management of patients with 'basal' tumors...

..In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours...

..In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R=2.29), MIB1 > 50 (R=3.80), ERBB2 negativity (R=2.24) and p53 positivity (RR=1.45)...

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..Interreader correlation was moderately good, and evidence of learning was seen. Equipment manufacturer, field strength, and age affected specificity but not sensitivity...

..In this issue of Cancer Cell, Gauthier and colleagues suggest that abrogated response to cell stress measured by analysis of p16 and the proliferation marker Ki67 accurately predicts recurrence in ductal carcinoma in situ...

..In a paper in this issue of Breast Cancer Research, Alowami has shown a relationship between density and stromal proteins, which might provide useful insight into mammographic density...

..In the context of screening, quantitative enhancement parameters appear to be less useful for lesion characterization...

..We report a case in which eruptive syringoma with clear cell morphology was found to express progesterone receptors, suggesting the possibility of hormonal control of the tumor...

..Scoring systems developed on one equipment software may not be transferable to other manufacturers...

..The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent...