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Excision repair cross‐complementation group 1 protein expression predicts survival in patients with high‐grade, non‐metastatic osteosarcoma treated with neoadjuvant chemotherapy
Author(s) -
Hattinger Claudia Maria,
Michelacci Francesca,
Sella Federica,
Magagnoli Giovanna,
Benini Stefania,
Gambarotti Marco,
Palmerini Emanuela,
Picci Piero,
Serra Massimo,
Ferrari Stefano
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12653
Subject(s) - osteosarcoma , chemotherapy , medicine , oncology , nucleotide excision repair , cancer research , biology , dna repair , gene , genetics
Aims To evaluate the clinical impact of excision repair cross‐complementation group 1 ( ERCC 1) 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 / SSG 1 validation set neoadjuvant chemotherapy protocols, based on the use of cisplatin, adriamycin, methotrexate, and ifosfamide. In the training set, ERCC 1 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, ERCC 1 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 ERCC 1 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 ERCC 1 and ABCB 1 expression showed that patients who were positive for both markers had a significantly worse prognosis. Conclusions The ERCC 1 level at diagnosis is predictive for the outcome of patients with non‐metastatic, high‐grade OS treated with neoadjuvant chemotherapy, and co‐evaluation with ABCB 1 can identify high‐risk groups of OS patients who are refractory to standard regimens.