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Decrease of survivin, p53 and Bcl-2 expression in chemorefractory colorectal liver metastases may be predictive of radiosensivity radiosensivity after radioembolization with yttrium-90 resin microspheres
- Source :
- Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 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.
- Subjects :
- Liver metastase
Microsphere
Male
p53
Cancer Research
Pathology
Proliferation index
Colorectal cancer
Survivin
Colorectal Neoplasm
Gastroenterology
Inhibitor of Apoptosis Proteins
Liver metastases
Yttrium Radioisotopes
Prospective Studies
Neoplasm Metastasis
Prospective cohort study
Yttrium-90-resin microspheres
medicine.diagnostic_test
biology
Liver Neoplasms
Middle Aged
Embolization, Therapeutic
Microspheres
Neoplasm Metastasi
Oncology
Proto-Oncogene Proteins c-bcl-2
Liver Neoplasm
Liver biopsy
Ki-67
Biomarker (medicine)
Female
Colorectal Neoplasms
Human
Adult
medicine.medical_specialty
Adolescent
Composite Resins
Young Adult
Yttrium Radioisotope
Internal medicine
Inhibitor of Apoptosis Protein
medicine
Humans
Bcl-2
Radioembolization
Aged
business.industry
Research
medicine.disease
Genes, p53
Composite Resin
Genes, bcl-2
Prospective Studie
biology.protein
Yttrium-90-resin microsphere
Steatohepatitis
Tumor Suppressor Protein p53
business
Subjects
Details
- ISSN :
- 17569966
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of experimentalclinical cancer research : CR
- Accession number :
- edsair.doi.dedup.....40688c34ca08278606f13b9cc453c74e