Characterization of CXCR4 Expression in Chondrosarcoma of Bone
S Bai, D Wang, MJ Klein, GP Siegal. University of Alabama at Birmingham, Birmingham, AL
Background: The CXCR4/SDF-1 system has been found to strongly correlate with neoplastic progression leading to metastases in a number of tumors including those of prostate, skin, breast, muscle, and bone. Increased CXCR4 mRNA expression in osteosarcoma tumor samples has previously been shown to correlate with reduced overall survival and with the presence of metastases at diagnosis. Excluding hematologic malignancies, chondrosarcoma (CS) of bone is the most common primary malignant tumor of bone, in adults in the U.S. Whether CXCR4 is detectable in CS and whether CXCR4 expression level correlates with CS grade, progression, and prognosis was the subject of this study.
Design: Archived materials from 22 CS samples banked between 2001 and 2006 were retrieved. All the slides were reviewed microscopically to confirm the initial diagnosis. The pathological features of the tumors were evaluated. Immunohistochemistry using monoclonal anti-CXCR4 antibody (R&D Systems) was performed on formalin-fixed, paraffin-embedded tissue sections and analyzed by histomorphometric techniques. Invasive ductal carcinoma of the breast was used as the positive control. All controls reacted appropriately.
Results: There were 14 high-grade (Grade II-III) CSs and 8 low-grade (Grade I) CSs. The 14 high-grade CS samples were derived from 12 patients. A single sample was provided by 18 patients and 2 samples were available from the remaining 2 patients. Of the study cohort, 10 were males and 10 females, ranging in age from 24 to 80 years. Follow-up ranged from 3 to 84 months. Essentially, all CS cells stained for CXCR4. However, the percentage of the positive area in the selected tumor fields between these two groups was significantly different, with significantly greater positivity in the high-grade tumors (p<0.001). More interestingly, the staining intensity of the CXCR4 between the two groups was also significantly different. There was a higher staining intensity in high grade CS cells (p<0.001). Neither recurrences nor metastasis were seen in the low grade group. 5 patients suffered a local recurrence and 2 had remote metastases in the high grade group. The CXCR4 expression levels increased in the recurrence/metastases samples for the 2 patients with more than one sample, indicating with progression of the tumor, the expression level of CXCR4 rises.
Conclusions: CXCR4 expression exists in all CS cells with its quantity and intensity increasing with progression which, in turn correlates with a poorer prognosis as assessed by recurrence or metastases.
Category: Bone & Soft Tissue
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 9, Tuesday Morning