SIRT2: tumour suppressor or tumour promoter in operable breast cancer?

PURPOSE: Sirtuins comprise a family of genes involved in cellular stress, survival and damage responses. They have been implicated in a range of diseases including cancer, with most information pertaining to their function in tumourigenesis being derived from in vitro studies, or model organisms. Their putative roles as tumour suppressors or tumour promoters remain to be validated in vivo. Little is known about their role in breast tumourigenesis. We sought to evaluate the seven sirtuin family members (SIRT1-7) in a human breast cancer cohort, in relation to clinico-pathological features and outcome of the disease. MATERIALS AND METHODS: Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in 392 oestrogen receptor (ER+ve) and 153 ER-ve breast tumour samples. SIRT1-7 transcriptional levels were assessed in normal (n=25), non-malignant (n=73) and malignant (n=70) breast tissue using Relative Quantitative Real Time PCR. Statistical analyses determined if SIRT1-7 transcription or protein expression was associated with clinical parameters or outcome. RESULTS: In ER-ve tumours, high protein levels of nuclear SIRT2 were associated with reduced time to recurrence and disease-specific death. This association was only observed in Grade 3 tumours. In the ER+ve cohort, high SIRT2 nuclear levels were associated with shorter disease-free survival and time to recurrence whilst on Tamoxifen, in patients with Grade 3 tumours. Conversely, in Grade 2 tumours, high SIRT2 levels were associated with increased time to recurrence. CONCLUSIONS: Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade.

Guideline for prophylactic feeding tube insertion in patients undergoing resection of head and neck cancers.

BACKGROUND: Supplementary nutrition is an important aspect of the multidisciplinary management of head and neck cancer patients. In our unit, method of feeding is based on an arbitrary predicted duration of overall treatment (<30 days indicates NG feeding, >30 days prophylactic PEG tube insertion is appropriate). This paper provides a guideline to assist in choosing the feeding method early on to avoid the need for later PEG insertion in those who were initially fed orally or via NG tube. PATIENTS AND METHODS: 59 patients undergoing resection of head and neck tumours were included, grouped according to their tumour stage and location. They were assessed pre- and post-operatively for 5 years and their diet consistency score, method of supplementary feeding and weight were noted. RESULTS: Mean prophylactic PEG feeding duration was 771 days (N = 12), these patients mostly had T3/T4 tumours involving the tongue. Mean NG duration was 30.5 days (N = 42), 15 later had PEG insertion at mean 47 days post-operatively, resulting in a total mean supplementary feeding duration of 579.6 days. These patients tended to have higher stage tumours and poorer pre-operative diet consistency scores. 43 patients required post-operative radiotherapy. This significantly increased feeding duration versus surgery alone, and therefore increases the likelihood of requiring PEG insertion. CONCLUSIONS: Based on our findings, we have constructed an algorithm to assist in determining which patients with operable head and neck cancer should have prophylactic PEG tube insertion.