Furthermore, several studies have shown an increased incidence of p53 nuclear accumulation

in liver metastases in comparison to the primary tumor, hypothesizing a role for p53 in CRC liver metastatization. In particular, the presence of ≥ 3 liver metastases identified a subset of patients with a very poor prognosis mainly when associated to p53 mutations [17]. A number of studies have also shown that tumors that do not express detectable levels of Bcl-2, but which exhibited nuclear accumulation of p53, were associated with the shortest patient survival, while Bcl-2-positive and p53-negative tumors had the best prognosis [12, 17]. Studies conducted at our Institute

showed that p53 positivity combined with Bcl-2 negativity and elevated Ki-67 score correlated with advanced tumor stage, poorly differentiated Cyclosporin A ic50 tumors and increased probability of selleck chemicals relapse. Also elevated survivin expression levels in primary CRC are related to decreased survival [14, 15]. In resected liver tumors, altered expression of survivin, p53, Ki-67 and, more recently, KRAS mutations, have been shown to be independently predictive of hepatic recurrence and poor survival [13, 16, 18]. It is recently reported that defective mismatch repair predicts resistance to 5-fluorouracil (5FU) and KRAS mutation resistance to anti-EGFR antibody therapy [19]. Nevertheless, no predictive markers of RE efficacy in mCRC have been identified Selleckchem NSC 683864 Suplatast tosilate up to now. In terms of the predictive response to radiotherapy, several studies have linked epidermal growth factor receptor (EGFR) and vascular endothelial

growth factor (VEGF) expression to a lack of response to pre-operative radiotherapy in locally advanced rectal cancer [19–21]. Neither p53, Ki-67 and survivin expression appear to be correlated to pre-operative chemo-radiotherapy response and prognosis in locally advanced rectal cancer [22, 23]. To date, however, no study has evaluated the predictive value of molecular markers on radiosensitivity of CRC liver metastasis. In this context, our findings, although in a very limited number of patients, may be clinically relevant. The rapid changes of biomarkers observed in our series post-90Y-RE may be due to clonal selection or to epigenetic changes, not previously recorded in this context. Such mechanisms are usually discussed in the context of cell adaption to chemotherapy and evolving resistance. Radio-sensitivity of colorectal cancer cells may be determined by p53 mutation [23, 24], whereas there is no evidence that chemotherapy per se cause changes in the cellular expression of p53 [25]. This is the first time that we have recorded a down-staging in p53 protein expression after 90Y-RE.