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
- Equal contributors
1 Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy
2 Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy
3 Department of Interventional Radiology, Regina Elena National Cancer Institute, Rome, Italy
4 Department of Surgery, Pascale Cancer Institute, Naples, Italy
5 Department of Interventional Radiology, Pascale Cancer Institute, Naples, Italy
6 Department of Interventional Radiology, Malpighi Hospital, Bologna, Italy
7 Biostatistics, Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy
8 Department of Nuclear Medicine, Regina Elena National Cancer Institute, Rome, Italy
9 Medical oncology, Regina Elena National Cancer Institute, Rome, Italy
Journal of Experimental & Clinical Cancer Research 2013, 32:13 doi:10.1186/1756-9966-32-13Published: 6 March 2013
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.