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

Journal of Experimental & Clinical Cancer Research

Marcella Mottolese²  Maria Grazia Diodoro⁸  Carlo Garufi³  Raffaello Mancini²  Rosa Sciuto⁶  Cristiana Ercolani²  Isabella Sperduti⁴  Emanuela Giampalma¹  Rita Golfieri¹  Francesco Fiore⁷  Francesco Izzo⁹  Giuseppe Pizzi⁵  Livio Carpanese⁵  Maurizio Cosimelli⁸  Elisa Melucci² 

[1] Department of Interventional Radiology, Malpighi Hospital, Bologna, Italy;Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy;Medical oncology, Regina Elena National Cancer Institute, Rome, Italy;Biostatistics, Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy;Department of Interventional Radiology, Regina Elena National Cancer Institute, Rome, Italy;Department of Nuclear Medicine, Regina Elena National Cancer Institute, Rome, Italy;Department of Interventional Radiology, Pascale Cancer Institute, Naples, Italy;Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy;Department of Surgery, Pascale Cancer Institute, Naples, Italy

关键词: Ki-67;    Bcl-2;    p53;    Survivin;    Yttrium-90-resin microspheres;    Radioembolization;    Liver metastases;    Colorectal cancer;   

Others  :  825353
DOI  :  10.1186/1756-9966-32-13

 received in 2013-02-04, accepted in 2013-02-27,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Melucci et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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