title: 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.
abstract: In a prospective multicenter phase II trial of radioembolization with yttrium-90 ((90)Y-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 (90)Y-RE.Of the 50 patients included in the study, 29 pre-(90)Y-RE therapy and 15 post-(90)Y-RE had liver biopsy specimens available. In these series we investigated survivin, p53, Bcl-2 and Ki-67 expression pre- and post-(90)Y-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-(90)Y-RE as compared to pre-(90)Y-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-(90)Y-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 (90)Y-RE therapy and may deserve further investigation on a larger series of patients.
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Melucci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cosimelli
authors.forename: Livio
authors.initials: L
authors.lastname: Carpanese
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pizzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Izzo
authors.forename: Francesco
authors.initials: F
authors.lastname: Fiore
authors.forename: Rita
authors.initials: R
authors.lastname: Golfieri
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giampalma
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Ercolani
authors.forename: Rosa
authors.initials: R
authors.lastname: Sciuto
authors.forename: Raffaello
authors.initials: R
authors.lastname: Mancini
authors.forename: Carlo
authors.initials: C
authors.lastname: Garufi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Diodoro
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D003188:Composite Resins / Q000008:administration & dosage; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult; D015021:Yttrium Radioisotopes / Q000008:administration & dosage*
chemical_list: C107489:BIRC5 protein, human; D003188:Composite Resins; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015021:Yttrium Radioisotopes