Expression of Smad and its signalling cascade in osteosarcoma.
OBJECTIVE
Smad signalling is important for inducing the expression of cell cycle inhibitors such as p21/WAF1, thereby facilitating transforming growth factor (TGF)-beta mediated inhibition of cell growth. The role and clinical implications of Smad signalling in osteosarcoma remain unclear.


METHODS
We assessed the immunohistochemical expression profiles of Smad2, P-Smad2, Smad4, and p21/WAF1 proteins in 34 cases of osteosarcoma. We also investigated whether the expression of these proteins was correlated with clinicopathological parameters.


RESULTS
The p21/WAF1 expression showed a significant relationship with tumour extension (p = 0.018). Smad4 expression was significantly correlated with Smad2 (p = 0.019) and P-Smad2 (p = 0.006) expression in osteosarcoma. Kaplan-Meier analysis showed that tumour extension (p = 0.0038), TNM stage (p = 0.0096), and p21/WAF1 expression (p = 0.0023) were significantly correlated with overall survival. Cox multivariate analysis showed that tumour extension (p = 0.048) and p21/WAF1 expression (p = 0.022) were independent poor prognostic factors.


CONCLUSIONS
Smad signalling in osteosarcoma is partially operative. The high p21/WAF1 expression in osteosarcoma is significantly correlated with tumour extension. Our results suggest that overexpression of p21/WAF1 in osteosarcoma might be one of the poor prognostic factors.
Won
Kyu Yeoun
KY
Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
Kim
Youn Wha
YW
Park
Yong-Koo
YK
D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051785:Smad Proteins