Showing papers by "Cheryl Gillett published in 2015"

Genomic complexity profiling reveals that HORMAD1 overexpression contributes to homologous recombination deficiency in triple-negative breast cancers

Abstract: Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination ...

Big Data: the challenge for small research groups in the era of cancer genomics.

Abstract: In the past decade, cancer research has seen an increasing trend towards high-throughput techniques and translational approaches. The increasing availability of assays that utilise smaller quantities of source material and produce higher volumes of data output have resulted in the necessity for data storage solutions beyond those previously used. Multifactorial data, both large in sample size and heterogeneous in context, needs to be integrated in a standardised, cost-effective and secure manner. This requires technical solutions and administrative support not normally financially accounted for in small- to moderate-sized research groups. In this review, we highlight the Big Data challenges faced by translational research groups in the precision medicine era; an era in which the genomes of over 75 000 patients will be sequenced by the National Health Service over the next 3 years to advance healthcare. In particular, we have looked at three main themes of data management in relation to cancer research, namely (1) cancer ontology management, (2) IT infrastructures that have been developed to support data management and (3) the unique ethical challenges introduced by utilising Big Data in research.

Digital imaging in the immunohistochemical evaluation of the proliferation markers Ki67, MCM2 and Geminin, in early breast cancer, and their putative prognostic value

Abstract: Immunohistochemical assessment of proliferation may provide additional prognostic information in early breast cancer However, due to a lack of methodological standards proliferation markers are still not routinely used for determining therapy Even for Ki67, one of the most widely-studied markers, disagreements over the optimal cutoff exist Improvements in digital microscopy may provide new avenues to standardise and make data more reproducible We studied the immunohistochemical expression of three markers of proliferation: Ki67, Mini-Chromosome Maintenance protein 2 and Geminin, by conventional light microscope and digital imaging on triplicate TMAs from 309 consecutive cases of primary breast cancers Differences between the average and the maximum percentage reactivity in tumour cell nuclei from the three TMA cores were investigated to assess the validity of the approach Time-dependent Receiver Operating Characteristic curves were utilized to obtain optimal expression level cut-offs, which were then correlated with clinico-pathological features and survival High concordance between conventional and digital scores was observed for all 3 markers (Ki67: rs = 087, P < 0001; MCM2: rs = 094, P < 0001; and Geminin: rs = 086, P < 0001; Spearman’s rank) There was no significant difference according to the number of TMA cores included for either Ki67 or MCM2; analysis of two or three cores produced comparable results Higher levels of all three proliferation markers were significantly associated with higher grade (P < 0001) and ER-negativity (P < 0001) Optimal prognostic cut-offs for percentage expression in the tumour were 8 %, 12 and 233 % for Ki67, MCM2 and Geminin respectively All 3 proliferation marker cutoffs were predictive of 15-year breast cancer-specific survival in univariable Cox regression analyses In multivariable analysis only lymph node status (HR = 39, 95 % CI = 179-85, P = 00006) and histological grade (HR = 184, 95 % CI = 1–338, P = 005) remained significantly prognostic Here we show that MCM2 is a more sensitive marker of proliferation than Ki67 and should be examined in future studies, especially in the lymph node-negative, hormone receptor-positive subgroup Further, digital microscopy can be used effectively as a high-throughput method to evaluate immunohistochemical expression

Concordance of intrinsic subtyping and risk of recurrence (ROR) scores between matched primary and metastatic tissue from Triple Negative Breast Cancer Trial (TNT).

Abstract: 1019 Background: The majority of triple negative breast cancers are of basal-like subtype (BLBC). There is uncertainty about concordance of intrinsic subtypes and ROR scores by PAM50 between matche...