Tumours arising in BRCA1 mutation carriers and sporadic basal-like breast carcinomas have similar phenotypic, immunohistochemical and clinical characteristics. SOX2 is an embryonic transcription factor located at chromosome 3q, a region frequently gained in sporadic basal-like and BRCA1 germline mutated tumours. The aim of the study was to establish whether sox2 expression was related to basal-like sporadic breast tumours. Two hundred and twenty-six sporadic node-negative invasive breast carcinomas were immunohistochemically analysed for oestrogen receptor (ER), progesterone receptor (PR), CK5/6, EGFR, vimentin, HER2, ki67, p53 and sox2 using tissue microarrays. Tumours were considered to have basal-like phenotype if they were ER/HER2-negative and CK5/6 and/or EGFR-positive. Thirty cases of this series (13.7%) displayed a basal-like phenotype. Sox2 expression was observed in 16.7% of cases and was significantly more frequently expressed in basal-like breast carcinomas (43.3% in basal-like, 10.6% in luminal and 13.3% in HER2 þ tumours, Po0.001). Moreover, Sox2 showed a statistically significant inverse association with ER and PR (P ¼ 0.001 and 0.017, respectively) and direct association with CK5/6, EGFR and vimentin (P ¼ 0.022, 0.005 and o0.001, respectively). Sox2 is preferentially expressed in tumours with basal-like phenotype and may play a role in defining their less differentiated/'stem cell' phenotypic characteristics. Modern Pathology (2007) 20, 474-481.

The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, and the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCI and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDC were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY (Oncocarta v 1.0 panel). Fluorescence in situ hybridization and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCI and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (ie 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations.

Studies of the electrocatalytic oxidation of β-nicotinamide adenine dinucleotide (NADH) at glassy carbon rotated disk electrodes modified with electrodeposited films derived from 3,4-dihydroxybenzaldehyde (3,4-DHB) indicate that the mechanism of such electrooxidation proceeds via the formation of an intermediate complex. The reaction also appears to be strongly influenced by the presence of Ca(2+) and Mg(2+) ions as well as by pH. Ascorbate can also be electrocatalytically oxidized at these modified electrodes, giving rise to an electrochemical response very similar to that obtained for NADH. Due to this similarity, the presence of ascorbate in NADH determinations presents a severe interference that cannot be mitigated on the basis of electrochemical responses alone. However, this interference effect can be virtually suppressed by the presence of ascorbate oxidase in solution or immobilized on a nylon mesh which, in turn, is in contact with the electrode modified with the film of 3,4-DHB. Using this approach, we describe the construction of an alcohol biosensor based on alcohol dehydrogenase and which is, furthermore, free from interference effects due to ascorbate.