Expression of cell cycle, angiogenesis and metastases associated factors in osteosarcoma - immunohistochemical analysis of tissue array in 35 patients

Abstract

10036 Background: Osteosarcoma is the most common, non-haemopoietic primary malignant tumor of bone. A variety of biological markers have been investigated for their prognostic value with variable results. This study is aimed to assess the prognostic and biological value of biological markers involved in cell cycle checkpoint regulation (p53 family, p16, and PTEN), cell adhesion, motility and invasion (ezrin and beta catenin), angiogenesis (VEGF and PlGF) in tumor samples of osteosarcoma patients. Methods: Thirty-five patients were chosen for the study (ages 6–74 years, median age - 15 years). Among them, 32 were high-grade conventional intramedullary osteosarcoma, and 3 were Paget osteosarcomas. Eight patients presented with metastases. Immunohistochemical analysis was performed on a tissue array of tumor samples with standard protocol. Clinical outcome was measured as events (metastasis or death), chemo-response (stage), and survival by multivariate analysis. Analysis also included our previous reported results of p53, p63 and p73. Results: Staining was assessed based upon semi-quantitative manual scoring. Appropriate staining (nuclear or cytoplasmic) of >5% in tumor cells was considered as positive for all markers. The percentage positivity for the markers is as follows: p53 =29%, p63 =37%, p73= 9%, p16 =60%, PTEN=83%, ezrin =77%, beta catenin =91%, VEGF= 86% and PlGF =54%. There was no association of marker expression with specific subtype or location. Statistical analysis revealed no significant association between the positivity of these markers with clinical outcomes. Expression of ezrin was observed in all eight patients with metastases, although this finding did not approach statistical significance (P = 0.15). There was significant association between ezrin and P63 (P < 0.05). Conclusions: 1. Expression of p53 family proteins, p16, PTEN, ezrin, beta catenin, VEGF, and PlGF are not significant predictors of clinical outcome in osteosarcoma patients. 2. Ezrin may be essential for osteosarcoma metastases. 3. No significant association between VEGF, PlGF and metastases. 4. The positive association between ezrin and P63 is interesting and need to be evaluated further. No significant financial relationships to disclose.