Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma.
OBJECTIVE
To investigate the immunohistochemical expression of three apoptosis-related genes (bax, bcl-2, and p53) and apoptosis (TUNEL) in patients with primary osteosarcoma, and examine potential correlations between gene expression and clinicopathological characteristics in these patients.


METHODS
Thirty-five primary osteosarcoma specimens and 18 tissue specimens deriving from non-malignant osseous lesions were immunohistochemically stained for bax, bcl-2, and p53 proteins, while apoptosis was investigated by the TUNEL method. The results were statistically analyzed.


RESULTS
P53, bax, and bcl-2 protein expression was observed in 22 (62.9%), 29 (82.9%), and 18 (51.4%) osteosarcoma patients, respectively. Non-specific positive TUNEL staining (+/-) was observed in two primary osteosarcoma cases (5.7%). None of the benign controls expressed any of the genes studied. None of the apoptosis-related genes studied was able to predict overall or disease-free survival in our group of patients. Nevertheless, increased bax/bcl-2 protein expression ratio was associated with a decreased 4-year survival and disease free survival (P = 0.0229 and P = 0.0370, respectively). Furthermore, all the patients who were bax(+)/bcl-2(-)/p53(+) relapsed within the 4-year follow-up period (P = 0.0385).


CONCLUSIONS
The increased apoptotic rate as determined by an elevated bax/bcl-2 protein expression ratio or by the bax(+)/bcl-2(-)/p53(+) protein expression pattern, appears to identify groups of osteosarcoma patients with unfavorable prognosis.
Kaseta
Maria-Kyriaki A
MK
First Department of Orthopaedic Surgery, KAT Hospital, University of Athens, Athens, Greece. labsures@med.uoa.gr
Khaldi
Lubna
L
Gomatos
Ilias P
IP
Tzagarakis
George P
GP
Alevizos
Leonidas
L
Leandros
Emmanuel
E
Papagelopoulos
Panayiotis J
PJ
Soucacos
Panayiotis N
PN
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein