TITLE:
TP53 Mutations and Chemotherapy Response to Neoadjuvant Metotrexate, Cisplatin and Adryamicin Chemotherapy in Resected Osteosarcoma
AUTHORS:
Ligia Richter, Marcelo Buzzi, Carmela Dantas-Barbosa
KEYWORDS:
Osteosarcoma; Chemoresistance; TP53 Gene
JOURNAL NAME:
International Journal of Clinical Medicine,
Vol.4 No.12A,
December
30,
2013
ABSTRACT: Osteosarcoma is a rare and highly
malignant tumor that usually affects adolescents and young adults. Despite current
management protocols, up to half of patients succumb to the disease. Moreover,
there is no well-characterized molecular marker for diagnosis and prognosis. TP53 alterations have been associated with a poor prognosis in
many cancers. The aim of this retrospective work was to find out whether TP53 functional status predicts response
to neoadjuvant chemotherapy and thus may help treatment decision for
osteosarcoma patients. Seventeen biopsies of osteosarcoma patients receiving
primary metotrexate, cisplatin and adryamicin chemotherapy followed by surgery
were analyzed. TP53
exons 5-9 mutations were
screened. Among 17 biopsies, 4 (23.5%) displayed TP53 mutations: 3 deletions and one single-nucleotide substitution.
The presence of TP53 gene mutation
does not correlate with resistance to chemotherapy according to histological
Rosen grade and nevertheless is associated with patient’s age in a significant manner (p 0.05). The presence of non-mutated TP53 is not entirely specific for a good
prognosis. We found no evidence that TP53
mutations predict chemoresistance in osteosarcoma patients more over the overall survival curve, followed
for more than 12 years,
showing no difference
between patients with tumors
harboring wild type or mutated TP53
gene (p 0.5). Further analysis to identify
other genes that can influence chemotherapy response and clinical outcome in osteosarcoma
is needed to improve patient treatment.