Evaluation of the Mitogen-Activated Protein Kinase Pathway in Osteosarcoma
Ki Yong Na, Youn Wha Kim, Yong-Koo Park. Kyung Hee University Hospital, Seoul, Republic of Korea
Background: The mitogen-activated protein kinase (MAPK) pathway has been implicated in the progression of osteosarcoma (OS). Recent studies have demonstrated that inhibitors of MAPK pathway components have antitumor activity in preclinical models of OS. However, less is known about the prognostic value of components of the MAPK pathway.
Design: We evaluated the expression of pan-Ras, Raf-1, pMEK1/2 and pERK1/2 in 61 patients with primary localized OS and assessed their prognostic influence on event-free survival (EFS) and overall survival (OVS) using immunohistochemistry.
Results: The markers pan-Ras, Raf-1, pMEK1/2 and pERK1/2 were expressed in 7 (11%), 36 (59%), 36 (59%) and 30 (49%) of 61 samples, respectively.
Patients whose tumors expressed Raf-1 or pMEK1/2 had poorer EFS and OVS than patients whose tumors showed negative staining for Raf-1 (P=0.016 and P=0.045, respectively) or pMEK1/2 (P=0.017 and P=0.047, respectively). Patients whose tumors stained positive for pERK1/2 had poorer OVS than the group whose tumors did not express pERK1/2 (P=0.026).
Notably, positive pMEK1/2 expression was predictive of shorter EFS and OVS (P=0.024 and P=0.042, respectively).
Conclusions: Our study provides further evidence that activation of the MAPK pathway plays a role in the aggressive behavior of OS. In addition, our study suggests that further investigation of MEK inhibitors in OS is warranted.
Category: Bone & Soft Tissue
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 7, Tuesday Morning