Cadherin-5: a biomarker for metastatic breast cancer with optimum efficacy in oestrogen receptor-positive breast cancers with vascular invasion

Background: A glycoproteomic study has previously shown cadherin-5 (CDH5) to be a serological marker of metastatic breast cancer when both protein levels and glycosylation status were assessed. In this study we aimed to further validate the utility of CDH5 as a biomarker for breast cancer progression. Methods: A nested case–control study of serum samples from breast cancer patients, of which n=52 had developed a distant metastatic recurrence within 5 years post-diagnosis and n=60 had remained recurrence-free. ELISAs were used to quantify patient serum CDH5 levels and assess glycosylation by Helix pomatia agglutinin (HPA) binding. Clinicopathological, treatment and lifestyle factors associated with metastasis and elevated biomarker levels were identified. Results: Elevated CDH5 levels (P=0.028) and ratios of CDH5:HPA binding (P=0.007) distinguished patients with metastatic disease from those that remained metastasis-free. Multivariate analysis showed that the association between CDH5:HPA ratio and the formation of distant metastases was driven by patients with oestrogen receptor (ER+) positive cancer with vascular invasion (VI+). Conclusions: CDH5 levels and the CDH5 glycosylation represent biomarker tests that distinguish patients with metastatic breast cancer from those that remain metastasis-free. The test reached optimal sensitivity and specificity in ER-positive cancers with vascular invasion.

Men’s strategies for preserving emotional well-being in advanced prostate cancer: an interpretative phenomenological analysis

Objective This study explores men with advanced prostate cancers’ own practices for promoting and maintaining emotional well-being using Interpretative Phenomenological Analysis. Design Five men with advanced prostate cancer participated in face-to-face, semi-structured, in-depth interviews. Results Within rich narratives of lost and regained well-being, two super-ordinate themes emerged – ‘living with an imminent and uncertain death’ and ‘holding on to life.’ Well-being was threatened by reduced sense of the future, isolation and uncertainty. Yet, the men pursued well-being by managing their emotions, striving for the future whilst enjoying life in the present, taking care of their families and renegotiating purpose. Running through participant’s accounts was a preference for taking action and problem-solving. Sense of purpose, social connectedness and life-engagement were revealed as concepts central to improving well-being, indicating areas which practitioners could explore with men to help them re-establish personal goals and life-purpose. Conclusions The findings also add weight to the evidence base for the potential value of psychological interventions such as cognitive behaviour therapy and mindfulness in men with prostate cancer.

HES1 in immunity and cancer

Hairy and enhancer of split homolog-1 (HES1) is a part of an extensive family of basic helix-loop-helix (bHLH) proteins and plays a crucial role in the control and regulation of cell cycle, proliferation, cell differentiation, survival and apoptosis in neuronal, endocrine, T-lymphocyte progenitors as well as various cancers. HES1 is a transcription factor which is regulated by the NOTCH, Hedgehog and Wnt signalling pathways. Aberrant expression of these pathways is a common feature of cancerous cells. There appears to be a fine and complicated crosstalk at the molecular level between the various signalling pathways and HES1, which contributes to its effects on the immune response and cancers such as leukaemia. Several mechanisms have been proposed, including an enhanced invasiveness and metastasis by inducing epithelial mesenchymal transition (EMT), in addition to its strict requirement for tumour cell survival. In this review, we summarize the current biology and molecular mechanisms as well as its use as a clinical target in cancer therapeutics.