The cortactin (CTTN) gene has been found, by transcriptomic
profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at
11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of
interest as a potential biomarker for osteosarcoma. MATERIALS AND METHODS:
Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy,
and paired with cell samples from normal tissue, prior to RNA expression analysis
on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was
analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233
tissue spots from 48 patients was used for an immunohistochemical (IHC) study of
cortactin. RESULTS: Transcriptomic profiling and real-time PCR analysis indicated
increased CTTN expression in osteosarcomas (p = 0.001, Student's T test). TMA IHC
showed cortactin to be present more frequently and in greater abundance in
osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney
test). Analysis of clinical outcomes indicated that overall survival for patients
with primary tumors positive for cortactin was significantly lower than that for
patients with cortactin negative (or only weakly staining) tumors (p = 0.0278,
Log-rank test). CONCLUSIONS: Our preliminary data support the hypothesis that
over-expression of cortactin, contained in the 11q13 amplicon, is involved in
osteosarcoma carcinogenesis. The potential of cortactin overexpression as a
biomarker for osteosarcoma is consolidated