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.
|