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

Elisa Melucci, Maurizio Cosimelli, Livio Carpanese, Giuseppe Pizzi, Francesco Izzo, Francesco Fiore, Rita Golfieri, Emanuela Giampalma, Isabella Sperduti, Cristiana Ercolani, Rosa Sciuto, Raffaello Mancini, Carlo Garufi, Maria Grazia Diodoro, Marcella Mottolese

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Abstract

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.

Original languageEnglish
Article number13
JournalJournal of Experimental and Clinical Cancer Research
Volume32
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Bcl-2
  • Colorectal cancer
  • Ki-67
  • Liver metastases
  • p53
  • Radioembolization
  • Survivin
  • Yttrium-90-resin microspheres

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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