Abstract
Purpose: Mutations of the TP53 gene have been associated with resistance to chemotherapy as well as poor prognosis in many different malignancies. This is the first prospective study of the prognostic value of somatic TP53 mutations in patients with newly diagnosed extremity osteosarcoma. Patients and Methods: One hundred ninety-six patients with high-grade, nonmetastatic osteosarcoma of the extremities were enrolled from seven tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 44 months). All patients received neoadjuvant or adjuvant chemotherapy and surgery. Tumors were analyzed for the presence of TP53 mutations by polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing. The association of the status of the 7P53 gene with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. Results: Patient age was the only factor that varied with TP53 gene status (P = .05). No relationship was identified between TP53 status and systemic relapse (relative risk, 1.24; P = .41). Analyses based on missense or nonsense mutations gave similar results (P > .10). In multivariate analysis, large (> 9 cm) tumor size (relative risk, 1.9; P = .006) and poor histologic response (≤ 90% necrosis) to chemotherapy (relative risk, 2.14; P = .02) were the only significant independent predictors of systemic outcome. Conclusion: We found no evidence that TP53 mutations predict for development of metastases in patients with high-grade osteosarcoma. Identification of other genes that influence chemotherapy response and clinical outcome in osteosarcoma is needed to facilitate further improvements in patient outcomes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1483-1490 |
| Number of pages | 8 |
| Journal | Journal of Clinical Oncology |
| Volume | 23 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2005 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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TP53 mutations and outcome in osteosarcoma : A prospective, multicenter study. / Wunder, Jay S.; Gokgoz, Nalan; Parkes, Robert; Bull, Shelley B.; Eskandarian, Sasha; Davis, Aileen M.; Beauchamp, Chris P.; Conrad, Ernest U.; Grimer, Robert J.; Healey, John H.; Malkin, David; Mangham, D. C.; Rock, Michael J.; Bell, Robert S.; Andrulis, Irene L.
In: Journal of Clinical Oncology, Vol. 23, No. 7, 2005, p. 1483-1490.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TP53 mutations and outcome in osteosarcoma
T2 - A prospective, multicenter study
AU - Wunder, Jay S.
AU - Gokgoz, Nalan
AU - Parkes, Robert
AU - Bull, Shelley B.
AU - Eskandarian, Sasha
AU - Davis, Aileen M.
AU - Beauchamp, Chris P.
AU - Conrad, Ernest U.
AU - Grimer, Robert J.
AU - Healey, John H.
AU - Malkin, David
AU - Mangham, D. C.
AU - Rock, Michael J.
AU - Bell, Robert S.
AU - Andrulis, Irene L.
PY - 2005
Y1 - 2005
N2 - Purpose: Mutations of the TP53 gene have been associated with resistance to chemotherapy as well as poor prognosis in many different malignancies. This is the first prospective study of the prognostic value of somatic TP53 mutations in patients with newly diagnosed extremity osteosarcoma. Patients and Methods: One hundred ninety-six patients with high-grade, nonmetastatic osteosarcoma of the extremities were enrolled from seven tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 44 months). All patients received neoadjuvant or adjuvant chemotherapy and surgery. Tumors were analyzed for the presence of TP53 mutations by polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing. The association of the status of the 7P53 gene with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. Results: Patient age was the only factor that varied with TP53 gene status (P = .05). No relationship was identified between TP53 status and systemic relapse (relative risk, 1.24; P = .41). Analyses based on missense or nonsense mutations gave similar results (P > .10). In multivariate analysis, large (> 9 cm) tumor size (relative risk, 1.9; P = .006) and poor histologic response (≤ 90% necrosis) to chemotherapy (relative risk, 2.14; P = .02) were the only significant independent predictors of systemic outcome. Conclusion: We found no evidence that TP53 mutations predict for development of metastases in patients with high-grade osteosarcoma. Identification of other genes that influence chemotherapy response and clinical outcome in osteosarcoma is needed to facilitate further improvements in patient outcomes.
AB - Purpose: Mutations of the TP53 gene have been associated with resistance to chemotherapy as well as poor prognosis in many different malignancies. This is the first prospective study of the prognostic value of somatic TP53 mutations in patients with newly diagnosed extremity osteosarcoma. Patients and Methods: One hundred ninety-six patients with high-grade, nonmetastatic osteosarcoma of the extremities were enrolled from seven tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 44 months). All patients received neoadjuvant or adjuvant chemotherapy and surgery. Tumors were analyzed for the presence of TP53 mutations by polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing. The association of the status of the 7P53 gene with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. Results: Patient age was the only factor that varied with TP53 gene status (P = .05). No relationship was identified between TP53 status and systemic relapse (relative risk, 1.24; P = .41). Analyses based on missense or nonsense mutations gave similar results (P > .10). In multivariate analysis, large (> 9 cm) tumor size (relative risk, 1.9; P = .006) and poor histologic response (≤ 90% necrosis) to chemotherapy (relative risk, 2.14; P = .02) were the only significant independent predictors of systemic outcome. Conclusion: We found no evidence that TP53 mutations predict for development of metastases in patients with high-grade osteosarcoma. Identification of other genes that influence chemotherapy response and clinical outcome in osteosarcoma is needed to facilitate further improvements in patient outcomes.
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U2 - 10.1200/JCO.2005.04.074
DO - 10.1200/JCO.2005.04.074
M3 - Article
VL - 23
SP - 1483
EP - 1490
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 7
ER -