Loyola University Chicago, USA
Title: Can we predict neoadjuvant therapy response in patients with osteosarcoma?
Osteosarcoma (OS) is a malignant primary tumor of bone affecting adolescents and young adults. There are few if any molecular markers to predict its behavior and prognosis. In our study we investigated the relationship of expression of different molecular markers in osteosarcoma tumors before treatment to pathologic necrotic response after neoadjuvant chemotherapy. In summary, deletion of RB1 (72%), gain of RUNX2 (68%), deletion of TP53 (52%), deletion 18q23 (48%) by molecular studies and p16-negative by IHC (38%) were common findings. Most abnormalities, particularly RB1 and TP53 deletions and RUNX2 gain, did not correlate with chemotherapy response. IHC p16-negative status correlated strongly with failed chemotherapy response (15/40). Alterations of 18q correlated slightly with poor response (p=0.0796). Poor response cases included 3 cases with deletion of 18q23, 3 cases with LOH for 18q23, and 1 case with copy gain (trisomy 18). Comparison of 18q genomic abnormalities in cases with a favorable versus poor response suggested a smallest region of overlap for a negative factor at 18q23. In conclusion we identified complex genotypes in the OS samples with frequent occurrence of previously identified biomarkers such as deletion RB1, deletion TP53, deletion 18q23 and gain of RUNX2. Comparison of genomic findings to p16-negative status and chemotherapy response revealed p16-negative status to be the best overall indicator of a poor chemotherapy response, with the poorest responders being both p16 negative and altered for 18q23. Additional studies are warranted to validate these findings and further characterize the role of CDKN2A and other factors that influence response to therapy in osteosarcoma patients.