Reassessment of alkaline phosphatase as serum tumor marker with high specificity in osteosarcoma

Abstract

The goal of this study was to reassess serum alkaline phosphatase (ALP) as tumor marker in osteosarcoma. We retrospectively examined serum ALP levels at diagnosis, every therapeutic step (neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy), metastasis, and follow‐up and analyzed the role of ALP as tumor marker in 210 osteosarcomas. The diagnostic performances of ALP were validated with pathology‐proven 899 other primary bone lesions. Elevated ALP at diagnosis was associated with inferior overall survival (OS) (Log Rank P < 0.001) and disease‐free survival (Log Rank P = 0.005) and independently significant for OS in multivariate analysis (hazard ratio [HR]=2.12, P = 0.032). During therapy, the ALP level significantly changed according to therapeutic steps (P < 0.001 for patients ≥15 years old, P < 0.001 for patients <15 years old) and survival (P = 0.015 for ≥15 years, P = 0.002 for <15 years), and the response of ALP to therapy and survival were associated (P = 0.042 for ≥15 years, P = 0.036 for <15 years). Initial ALP level was linearly correlated with tumor burden (total tumor volume; P = 0.016 for ≥15 years, bone tumor volume; P = 0.012 for ≥15 years). The sensitivity and specificity of ALP on diagnosis were 53.2% (95% Confidence Interval [CI]: 0.475–0.586) and 90.1% (95% CI: 0.888–0.913). The sensitivity of ALP on metastasis was 53.2% (95% CI: 0.431–0.624), and the specificity was 78.2% (95% CI: 0.720–0.839) at15 months postoperative and 90.0% (95% CI: 0.824–0.952) at 3 years postoperative. Serum ALP was found to be a valuable tumor marker with high specificity in osteosarcoma.

Novel classifiers with clinical laboratory parameters for early detection of osteosarcoma

“…Therefore, the specificity of ALP was unsatisfactory for OS diagnosis. In addition, previous studies have described the low sensitivity of ALP to detect OS . Consistently, our study discovered that ALP was less sensitive and specific than our established classifiers to distinguish all OS patients from HCs and patients with primary benign bone lesions.…”

“…Regarding OS, serum alkaline phosphatase (ALP) is probably one of the most well‐known tumor markers. Numerous studies have shown that pre‐treatment serum ALP, as well as its changes during therapeutic process, is a critical prognostic indicator for chemotherapy response, skeletal and lung metastases, and survival of OS patients . In addition, it has been known for a long time that OS patients often have higher serum ALP than normal subjects and patients with benign bone lesions, and ALP might help to diagnose OS initially.…”

“…In addition, it has been known for a long time that OS patients often have higher serum ALP than normal subjects and patients with benign bone lesions, and ALP might help to diagnose OS initially. However, there were still a large part (>40%) of OS patients with normal ALP levels, resulting in very low sensitivity for ALP in OS diagnosis …”

Clinical significance of serum soluble B7-H3 in patients with osteosarcoma

“…Although biomarkers are increasingly used in cancer treatment to refine risk stratification and augment current clinical decision making tools, there is still absent suitable and useful biomarkers for detecting OS in clinic [ 9 , 10 ]. For now, alkaline phosphatase (ALP), has been widely applied in clinic and known as a standard tumor biomarker of osteosarcoma, however, sometimes it provides false positives since ALP would be elevated in children after bone damage [ 11 , 12 ]. Other tumor markers, such as CA125 and CA199, were auxiliary evaluated the status of OS patients, however, these levels in the peripheral blood of OS patients are increased to varying degrees [ 13 , 14 ].…”

The Role of Osteocalcin and Alkaline Phosphatase Immunohistochemistry in Osteosarcoma Diagnosis

“…Alkaline Phosphatase (ALP) is an ubiquitous enzyme present in all tissues but is mainly concentrated in the liver, kidney, placenta, and bone. In the musculoskeletal system, ALP is abundant in osteoblasts and is considered to play a role in the mineralization of newly formed bone [ 10 ]. In the research conducted on canine, ALP is a sensitive and specific marker in identifying tumour cells in OSA [ 11 – 13 ].…”