Excision repair cross-complementation group 1 protein expression predicts survival in patients with high-grade, non-metastatic osteosarcoma treated with neoadjuvant chemotherapy

Claudia Maria Hattinger, Francesca Michelacci, Federica Sella, Giovanna Magagnoli, Stefania Benini, Marco Gambarotti, Emanuela Palmerini, Piero Picci, Massimo Serra, Stefano Ferrari

Research output: Contribution to journalArticle

Abstract

Aims: To evaluate the clinical impact of excision repair cross-complementation group 1 (ERCC1) expression in high-grade osteosarcoma (OS). Methods and 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.

Original languageEnglish
Pages (from-to)338-347
Number of pages10
JournalHistopathology
Volume67
Issue number3
DOIs
Publication statusPublished - Sep 1 2015

Keywords

  • ABCB1 protein
  • Cisplatin
  • ERCC1 protein
  • Immunohistochemistry
  • Osteosarcoma
  • Prognosis

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

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