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Connective Tissue Oncology Society

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Posters— Diagnostic Imaging/Pathology

MOLECULAR PREDICTORS OF OUTCOME IN PATIENTS WITH OSTEOSARCOMA

Reith JD, Casanova J, Berrey BH, Enneking WF, Scarborough MT (University of Florida, Gainesville, FL 32610)


Background: A variety of molecular markers related to survival, including bcl-2, p53, p-glycoprotein, CD95 (Fas), CD95-ligand (Fas-L), CD44, and CD44v, have been studied in a variety of human neoplasms, particularly carcinomas. Their significance in patients with osteosarcoma is largely unknown. The purpose of this archival study was to determine if there is a correlation between expression of these factors and disease free and overall survival for patients with osteosarcoma.

Patients and Methods: All patients had stage IIB osteosarcomas originating around the knee (distal femur, proximal tibia). Group A included 20 patients who underwent biopsy and were treated with neoadjuvant chemotherapy and surgical resection. Group B included 73 patients who underwent primary surgical resection of their tumor followed by postoperative chemotherapy. Tumors were evaluated with antibodies to bcl-2, p53, Fas, Fas-L, CD44, CD44v6, and p-glycoprotein using standard avidin-biotin complex methods. Expression of the various antigens was compared to disease-free and overall survival, accounting for percent necrosis (Group A) and margin status (Groups A & B).

Results:

Antibody
Total positive
Group A
Group B
p value
bcl-2
0/93
0/20
0/73
Not significant
p53
17/93 (18%)
6/20 (30%)
13/73 (15%)
Not significant
CD95
9/93 (10%)
1/20 (5%)
8/73 (11%)
p<0.05
CD95-L
52/93 (56%)
16/20 (80%)
36/73 (49%)
Not significant
CD44
28/93 (30%)
11/20 (55%)
17/73 (23%)
Not significant
CD44V6
13/93 (14%)
6/20 (30%)
7/73 (10%)
p<0.03
P-glycoprotein
46/93 (49%)
8/20 (40%)
38/73 (52%)
p=0.10

Conclusions: CD95 appears to have a “protective” function in patients with osteosarcoma, probably by allowing tumor cells to proceed through apoptosis pathways to cell death. Although CD44v6, a vascular adhesion molecule, was identified in only 14% of the total cases, its expression correlated with subsequent development of metastases and death (11 of 13 patients developed pulmonary metastases, 10 dying of disease). Although p-glycoprotein did not reach statistical significance, there was a trend toward death from disease in patients expressing it.


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