Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells.
Consensus abstractBackground: The management of primary rectal cancer beyond total mesorectal excision planes (PRCbTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Methods: Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web- Executive summaryThe executive summary supports the need for standardization of care and a collaborative, cross-discipline consensus statement. Burden of disease:There are 14 000 new rectal cancers per year in the UK, 40 000 in the USA and under half a million new cases per year globally. Of these, 5-10 per cent have invaded adjacent organs at presentation and 10 per cent recur following primary surgery. Complexity of surgery:Major, exenterative, multivisceral resections require specialist multiprofessional care. The surgical procedures are time-consuming (up to 12 h) and are associated with prolonged length of hospital stay (between 10 and 30 days). Long-term 5-year survival rates vary between 30 and 50 per cent. Adverse event rates have been reported in up to 50 per cent of patients. Superspecialist training of surgeons within a multidisciplinary team is required. Inappropriate worldwide variation in practice:There is a wide range of practice from non-specialist and specialist centres, with unequal access to care across global settings. These include differing referral selection criteria, where patients are often denied potentially curative treatment. When surgery is offered, the outcome is neither captured by the national databases nor audited locally. * Collaborating members are shown at the end of the article. 1010The Beyond TME Collaborative Standardization of definitions: Definitions for the rectum, for primary rectal cancer beyond conventional total mesorectal excision planes, and for recurrent rectal cancer have been defined heterogeneously in the literature and between different institutions, leading to a clear requirement for standardization of the exact definition of these terms.The need for policy: Delay in diagnosis is common and inequalities exist in referral patterns based on geography, with no clear clinical guidelines. No current guidelines exist for these patients, despite the significant burden, cost of surgery, morbidity and national variations in care.Resource impact: The cost-effectiveness of the complex assessments and interventions requires further research. The quality of life and morbidity from non-operative management are unknown. There is a need for specialist training of the mul...
In early experience, RRC appears to be feasible and a safe alternative to the ORC. RRC appears to have lower high-grade complications and mortality rates compared with the open approach. Although these results are promising, the authors would suggest caution while interpreting these results due to concerns with methodological flaws in the included studies in this review.
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