Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases.
OBJECTIVE
To identify candidate prognostic biological markers useful in selecting high-risk patients with classic primary giant cell tumours (GCT). GCT specimens with different behaviour associated with an increased risk of local and/or distant relapses were studied.


RESULTS
Screening mRNA microarray analysis followed by real-time polymerase chain reaction and immunohistochemistry on tissue microarray sections was used to validate the prognostic role of differentially expressed genes on a larger series by statistical analysis tests. Global gene expression profiling identified 109 differentially expressed genes according to prognosis. A correlation was found between mRNA levels and clinical outcome identifying Tenascin C (TNC) as the most significant prognostic biological marker. By means of backward Wald logistic regression, TNC overexpression defined an eightfold increased risk for metastasis and fourfold for local recurrence. At the protein level, TNC immunoreactivity resulted in a significant difference in the disease-free survival probability curves, providing a stratification for GCT patients, useful for predicting relapse.


CONCLUSIONS
Our study provides important data for the selection of biomarkers with a significant clinical impact and suggests the importance of TNC expression in identifying GCT patients at a higher risk of relapse for closer follow-up and adjuvant medical therapy.
Pazzaglia
Laura
L
Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, University of Bologna, Bologna, Italy. laura.pazzaglia@ior.it
Conti
Amalia
A
Chiechi
Antonella
A
Novello
Chiara
C
Magagnoli
Giovanna
G
Astolfi
Annalisa
A
Pession
Andrea
A
Krenacs
Tibor
T
Alberghini
Marco
M
Picci
Piero
P
Benassi
Maria Serena
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012307:Risk Factors; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019063:Tenascin