ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma.
BACKGROUND
It has been reported that the c-erbB-2 protooncogene is frequently amplified and overexpressed in many types of cancers, except sarcomas and hematological malignancies.


METHODS
Expression of ErbB-2 in the tumors of 26 patients with conventional osteosarcoma was evaluated by immunoblotting. DNA from osteosarcoma tissues that expressed ErbB-2 were analyzed by Southern blot hybridization to examine gross rearrangement of the gene. The DNA was also surveyed for the presence of genetic mutation in the transmembrane domain of ErbB-2 by polymerase chain reaction-single-stranded DNA conformation polymorphism analysis. In addition, possible correlation of ErbB-2 expression with gender, age, histopathologic subtype, and response to chemotherapy was analyzed. Survival analysis was performed by the Kaplan-Meier test using the approximate chi-square statistic for the log-rank test.


RESULTS
The ErbB-2 protein was detected in 11 of 26 osteosarcoma tissues (42%) by immunoblot analysis. Expression of ErbB-2 was confirmed by immunohistochemical studies using specific anti-ErbB-2 monoclonal antibody. However, neither amplification of the c-erbB-2 gene nor evidence of significant genetic mutation was found in these osteosarcomas. Expression of ErbB-2 examined by immunoblotting was most strongly correlated with early pulmonary metastases (P < 0.05). Among the entire group of 26 patients in this study, Kaplan-Meier life table survival of the patients with apparent ErbB-2 expression was significantly worse than that of the patients with little ErbB-2 expression (P < 0.01).


CONCLUSIONS
In 42% of the osteosarcomas, the tumor cells expressed ErbB-2. Expression of ErbB-2 was strongly correlated with early pulmonary metastasis and poor survival rate for the patient. These data suggest that ErbB-2 plays a significant role in aggressive tumor growth and in the promotion of metastatic potential in osteosarcomas. ErbB-2 in the osteosarcoma tissues would be a useful prognostic marker for patients.
Onda
M
M
Department of Oncology, University of Tokyo, Shirokanedai, Japan.
Matsuda
S
S
Higaki
S
S
Iijima
T
T
Fukushima
J
J
Yokokura
A
A
Kojima
T
T
Horiuchi
H
H
Kurokawa
T
T
Yamamoto
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000235:genetics* / Q000401:mortality; D002648:Child; D004277:DNA, Single-Stranded / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000302:isolation & purification*; D016019:Survival Analysis
D004277:DNA, Single-Stranded; D018719:Erb-b2 Receptor Tyrosine Kinases