Decrease of survivin,p53 and Bcl-2 expression in chemorefractory colorectal liver metastases may be predictive of radiosensivity after radioembolization with yttrium-90 resin microspheres

In a prospective multicenter phase ii trial of radioembolization with yttrium-90 (90y-re) in chemorefractory liver-dominant metastatic colorectal cancer (mcrc),we showed that median survival was 12.6 months (95% ci 7.0-18.3) with 48% of 50 patients achieving disease control. in this extension retrospective study,we analyzed whether a panel of biomarkers,known to be associated to an adverse clinical outcome,underwent variations in crc liver metastases pre and post 90y-re.of the 50 patients included in the study,29 pre-90y-re therapy and 15 post-90y-re had liver biopsy specimens available. in these series we investigated survivin,p53,bcl-2 and ki-67 expression pre- and post-90y-re by immuhistochemistry (ihc). our findings evidenced a decrease of survivin (77% vs 33%),p53 (93% vs 73%),bcl-2 (37% vs 26%) expression as well as of ki-67 proliferation index (62.5% vs 40%) on liver biopsies collected post-90y-re as compared to pre-90y-re. in the subset of 13 matched liver metastases we further confirmed the reduction of survivin (92.3% vs 53.8%; p = 0.06),p53 (100% vs 69.2%; p = 0.05) and bcl-2 (69.2% vs 53.8%; p = 0.05) expression post- 90y-re. this biomarker modulation was accompanied by morphological changes as steatohepatitis,hepatocyte necrosis,collagen deposition,proliferating and/or bile duct ectasia,focal sinusoidal dilatation and fibrosis.although our analysis was conducted in a very limited number cases,these changes appear strictly related to the response to 90y-re therapy and may deserve further investigation on a larger series of patients. © 2013 melucci et al; licensee biomed central ltd.