Journal des biomarqueurs moléculaires et du diagnostic

Molecular Reclassification in Pediatric Osteosarcomas at Surgical Resection is a Potential Helpful Prognostic Marker

Abstract

Lasthaus Christelle, Litzler Marie, Marcellin Luc, Chenard Marie-Pierre, Marec-Berard Perrine, Tabone Marie-Dominique, Pacquement Hélène, Brugières Laurence, Guenot Dominique and Entz-Werlé Natacha

Introduction: The management of pediatric high grade osteosarcoma is lacking new approaches to classify closely the patients and adapt thereafter the treatment initially or post-operatively. The objective of this study was to estimate the impact of the tumor molecular response comparatively to initial biopsy and to see if this molecular analysis was correlated to the histological response to neoadjuvant chemotherapy and/or prognosis.

Material and methods: 33 patients were included and allelotyping analyses using 23 micro satellites were performed on biopsy’s and tumor’s DNA versus normal blood DNA. Allelic imbalances were detected in all biopsy samples and the number of persistent AIs or not were quantified on tumors after pre-operative chemotherapy.

Results: We identified 4 subgroups with a significant impact on survival. The first group presents a complete disappearance of the AIs and a complete response independently from the histopathologic measure for tumor necrosis. The second group showed a partial response with persistence of some rearrangements after treatment. The third and the last one were characterized by the same molecular profile even more rearrangements, allowing to considered those subgroups as highly resistant osteosarcomas. This molecular re-stratification was associated with a significant impact on survival and provides evidence that this new approach on tumor resection might be a complementary and useful tool combined with histological response assessment.