Cytochrome P450 CYP3A4/5 Expression as a Biomarker of Outcome in Osteosarcoma

Purpose: Osteosarcoma, the most common pediatric primary bone tumor, is an aggressive malignancy with a tendency for early pulmonary metastasis. A reliable biomarker to predict clinical outcome at diagnosis has not yet been identified. To date, pathological review of neoadjuvant chemotherapy–induced necrosis is the most useful determinant of which patients are likely to develop metastatic disease. There is a clinical need to identify patients who will benefit from more aggressive preoperative therapy or perhaps require less aggressive chemotherapy. More than 30 human P450 isoenzymes have been characterized, with at least nine possessing some clinical relevance. One of these, CYP3A4/5 is involved in metabolic activation and detoxification of a wide number of carcinogens and chemotherapeutic agents, including many drugs that are useful in the treatment of osteosarcomas. Materials and Methods: Osteosarcoma tissue microarray blocks containing biopsies from 18 primary tumors were used to analyze the expression...