Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma.
BACKGROUND
Investigation of the relation between primary tumor and metastatic disease is necessary for the identification of predictive factors for postrecurrence survival (PRS) in patients with recurrent osteosarcoma.


METHODS
Cellular levels of P-glycoprotein, ErbB-2, p53, and Bcl-2 expression were evaluated in primary tumor biopsy and metachronous pulmonary metastasis specimens from 19 patients with high-grade osteosarcoma. Results were analyzed for differences between primary tumor and pulmonary metastases and for correlations between expression patterns and survival.


RESULTS
Positive staining in lung metastases was noted in 68%, 53%, 32%, and 84% of patients for P-glycoprotein, ErbB-2, p53, and Bcl-2, respectively. These percentages were higher than those observed in primary tumor specimens for all genetic markers evaluated, with a significant difference in the percentage of patients with positive staining for P-glycoprotein (68% vs. 32%; P = 0.05) and a near-significant difference in the percentage of patients with positive staining for Bcl-2 (84% vs. 53%; P = 0.08). Patients with ErbB-2 expression in the primary tumor were more likely to have multiple metastases and shorter recurrence-free intervals compared with patients in whom ErbB-2 expression was not observed, whereas differences in P-glycoprotein, p53, and Bcl-2 expression were not related to differences in metastatic pattern. PRS was influenced by p53 expression levels in pulmonary metastases, with patients who had negative staining for p53 having a significantly better PRS rate relative to patients with positive staining for p53 (3-year PRS rate: p53-negative, 64%; p53-positive, 17%; P = 0.008).


CONCLUSIONS
In the current study of patients with high-grade osteosarcoma, most patients exhibited increased cellular expression of P-glycoprotein, ErbB-2, and Bcl-2 in recurrent pulmonary metastases compared with primary tumor. Further studies aimed at investigating the relation between altered p53 expression in lung metastases and postrecurrence survival are recommended.
Ferrari
Stefano
S
Chemotherapy Service, Department of Musculoskeletal Oncology, Istituti Ortopedici Rizzoli, Bologna, Italy. stefano.ferrari@ior.it
Bertoni
Franco
F
Zanella
Licciana
L
Setola
Elisabetta
E
Bacchini
Patrizia
P
Alberghini
Marco
M
Versari
Michela
M
Bacci
Gaetano
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D002648:Child; D015331:Cohort Studies; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000556:secondary* / Q000628:therapy; D008297:Male; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000401:mortality* / Q000556:secondary* / Q000628:therapy; D011336:Probability; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53