Association of Pre-Chemotherapy Serum Alkaline Phosphatase Levels and p53 Protein Expression with Huvos Tumor Necrosis Grading in High-Grade Osteosarcoma: An Indonesian Tertiary Referral Center Experience
DOI:
https://doi.org/10.37275/bsm.v10i10.1672Keywords:
Alkaline Phosphatase, Huvos Grading, Neoadjuvant Chemotherapy, Osteosarcoma, p53 proteinAbstract
Background: High-grade osteosarcoma shows unpredictable chemosensitivity. Whether pre-chemotherapy serum alkaline phosphatase (ALP) and immunohistochemical p53 expression forecast post-neoadjuvant histopathological tumor necrosis remains contested in resource-constrained settings.
Methods: In a hospital-based nested cohort, 14 consecutive patients with primary high-grade extremity osteosarcoma (Palembang, 2023–2025) received three cycles of standardized neoadjuvant chemotherapy before wide resection. Pre-chemotherapy serum ALP and immunohistochemical nuclear p53 were related to Huvos response, dichotomized as poor (<90% necrosis; grades I–II) or good (≥90%; grades III–IV), using Fisher’s exact test, risk and odds ratios, and ROC analysis.
Results: The cohort comprised 9 males (64.3%) and 5 females (35.7%), mean age 22.0 ± 10.7 years. Poor histological response occurred in 11 patients (78.6%) and good response in 3 (21.4%). Elevated baseline ALP (>104 U/L) occurred in 92.9%, and p53 immunoreactivity was positive in 78.6%. Baseline serum ALP was not significantly associated with Huvos response (76.9% poor in elevated vs. 100.0% in normal; Fisher’s exact p = 1.000; RR = 0.769, 95% CI: 0.571–1.036), nor was p53 (81.8% poor in p53-positive vs. 66.7% in p53-negative; p = 1.000; OR = 2.250, 95% CI: 0.130–38.811; RR = 1.227, 95% CI: 0.526–2.864). ROC analysis for serum ALP yielded an AUC of 0.515 (95% CI: 0.205–0.825, p = 0.938), equivalent to random classification. An empirical cutoff of 176.5 U/L showed 100.0% specificity but only 36.4% sensitivity.
Conclusion: Pre-chemotherapy serum ALP and immunohistochemical p53 expression fail to predict post-neoadjuvant histopathological tumor necrosis in osteosarcoma, and cannot substitute for microscopic Huvos grading in guiding adjuvant treatment.
Authors
- Davin Caturputra Setiamanah1*
- Primadika Rubiansyah1
- Debby Handayati Harahap2
- 1Department of Orthopaedic and Traumatology, Faculty of Medicine, Universitas Sriwijaya / Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia
- 2Department of Pharmacology, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia
Corresponding author Davin Caturputra Setiamanah — davincsetiamanah@gmail.com
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Copyright (c) 2026 Davin Caturputra Setiamanah, Primadika Rubiansyah, Debby Handayati Harahap
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