Open Access Research

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 Melucci1, Maurizio Cosimelli2, Livio Carpanese3, Giuseppe Pizzi3, Francesco Izzo4, Francesco Fiore5, Rita Golfieri6, Emanuela Giampalma6, Isabella Sperduti7, Cristiana Ercolani1, Rosa Sciuto8, Raffaello Mancini1, Carlo Garufi9, Maria Grazia Diodoro2, Marcella Mottolese1* and Italian Society of Locoregional Therapies in Oncology (S.I.T.I.L.O.)

  • * Corresponding author: Marcella Mottolese mottolese@ifo.it

  • † Equal contributors

Author Affiliations

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

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Journal of Experimental & Clinical Cancer Research 2013, 32:13  doi:10.1186/1756-9966-32-13

Published: 6 March 2013

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.

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