title: Excision repair cross-complementation group 1 protein expression predicts survival in patients with high-grade, non-metastatic osteosarcoma treated with neoadjuvant chemotherapy.
abstract: OBJECTIVE
  To evaluate the clinical impact of excision repair cross-complementation group 1 (ERCC1) expression in high-grade osteosarcoma (OS).
  
  
  RESULTS
  Immunohistochemistry was performed on biopsies from 99 OS patients enrolled in the ISG/OS-Oss training set or ISG/SSG1 validation set neoadjuvant chemotherapy protocols, based on the use of cisplatin, adriamycin, methotrexate, and ifosfamide. In the training set, ERCC1 positivity was found in eight of 31 (26%) patients, and was significantly associated with worse event-free survival (EFS) (P = 0.042) and overall survival (OVS) (P = 0.001). In the validation set, ERCC1 positivity was found in 22 of 68 (32%) patients, and its significant associations with poorer EFS (P = 0.028) and OVS (P = 0.022) were confirmed. Multivariate analyses performed on the whole patient series indicated that ERCC1 positivity was the only marker that was significantly associated with a higher risk of worse prognosis, in terms of both EFS and OVS (P = 0.013). Co-evaluation of ERCC1 and ABCB1 expression showed that patients who were positive for both markers had a significantly worse prognosis.
  
  
  CONCLUSIONS
  The ERCC1 level at diagnosis is predictive for the outcome of patients with non-metastatic, high-grade OS treated with neoadjuvant chemotherapy, and co-evaluation with ABCB1 can identify high-risk groups of OS patients who are refractory to standard regimens.
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Claudia Maria
authors.initials: CM
authors.lastname: Hattinger
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Michelacci
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sella
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Magagnoli
authors.affiliation: Anatomy and Pathological Histology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Benini
authors.affiliation: Anatomy and Pathological Histology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gambarotti
authors.affiliation: Chemotherapy Ward of Muscoloskeletal Tumours, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Palmerini
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.affiliation: Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
authors.affiliation: Chemotherapy Ward of Muscoloskeletal Tumours, Orthopaedic Rizzoli Institute, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004317:Doxorubicin; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate
keywords: ABCB1 protein; ERCC1 protein; cisplatin; immunohistochemistry; osteosarcoma; prognosis