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Abstract: Proteomics, which is the global analysis of protein expression in cells and tissues, has emerged over the last ten to fifteen years as a key set of technologies to improve our understanding of disease processes and to identify new diagnostic, prognostic and predictive disease biomarkers. Whilst most proteomic studies have been conducted on fresh frozen tissue, the continuous improvements in technical procedures for protein extraction and separation, coupled with increasingly powerful bioinformatics, have provided the opportunity for proteomic analysis to be conducted on formalin-fixed wax-embedded tissue. This potential advance should allow proteomic analysis to be performed on the extensive archives of clinically annotated formalin fixed wax embedded tissue blocks stored in pathology departments worldwide. In this review the main techniques and their limitations involved in proteomic analysis of formalin fixed wax embedded tissue will be outlined and examples of their successful application will be indicated. [Copyright &y& Elsevier]

The potential of proteomic approaches to elucidate disease pathogenesis and biomarker discovery is increasingly being recognised. These studies are usually based on the use of fresh tissue samples. Problems in obtaining and storing fresh frozen samples, especially either for the investigation of rare diseases or for the study of microscopic disease foci, have led to the investigation of the possible use of formalin fixed wax embedded tissue for proteomic biomarker detection Overcoming problems with protein cross-linking associated with formalin fixation of tissues, especially by using heat-mediated retrieval techniques combined with highly sensitive methods for protein separation and identification are now emerging, giving promise to the use of formalin fixed wax embedded tissues for proteomic analysis. Formalin fixed wax embedded tissues, together with their associated clinical and pathological information outcome may provide significant potential opportunities for proteomics research. Such studies of formalin fixed wax embedded tissue will allow access to already acquired clinical tissue samples which can be readily correlated with clinical, pathological and outcome data. It also provides access to rare types of tissue/diseases that would be either difficult to collect prospectively in a timely manner or are unlikely to be available as fresh samples. The purpose of this review is to provide an overview of the issues associated with the use of formalin fixed wax embedded tissues for proteomics. [ABSTRACT FROM AUTHOR]

Aims bcl-2-associated transcription factor 1 ( BCLAF1) is a nuclear protein that binds to bcl-related proteins and can induce apoptosis and autophagy. The aim of this study was to investigate the expression of BCLAF1 in a series of rectal cancers following neoadjuvant therapy. Methods and results Immunohistochemistry was performed on a post-neoadjuvant therapy rectal cancer tissue microarray. It contained rectal cancers ( n = 248), lymph node metastases ( n = 76), and non-neoplastic rectal mucosal samples ( n = 73). A monoclonal antibody against BCLAF1 that we have developed was used. Non-neoplastic rectal epithelium showed nuclear localization of BCLAF1 in both crypt and surface epithelial cells, whereas rectal cancers showed both nuclear and cytoplasmic BCLAF1 expression. Most rectal cancers showed moderate or strong nuclear immunoreactivity, but showed weak cytoplasmic immunoreactivity. Cytoplasmic BCLAF1 expression was increased in primary rectal cancers as compared with non-neoplastic rectal mucosa ( P = 0.008). Negative and weak nuclear BCLAF1 expression was associated with a poor prognosis [hazard ratio ( HR) 0.502, 95% confidence interval ( CI) 0.269-0.939, χ2 = 4.876, P = 0.027]. Nuclear BCLAF1 expression was independently prognostic in a multivariate model ( HR 0.431, 95% CI 0.221-0.840, P = 0.013). Conclusions This study has shown that both cytoplasmic BCLAF1 expression and nuclear BCLAF1 expression are increased in post-neoadjuvant therapy rectal cancer, and that negative and weak nuclear BCLAF1 expression are independently associated with a poor prognosis. [ABSTRACT FROM AUTHOR]