Osteosarcoma is the most common primary malignancy of bone in children and young adults. Necrotic response in the tumor specimen after preoperative chemotherapy is a reproducible and reliable prognostic marker for survival in patients with OS. Pathologic tumor necrosis 90% or greater in the surgical specimen has been correlated with a 5-year survival of 75% to 90%. Although several molecular markers, including P-glycoprotein, Ki-67, p53, ezrin and HER2 have been associated with OS, a clear consensus has not emerged regarding the prognostic and predictive significance. The downregulation of p16 INK4A proteins is found in around 60% of high-grade osteosarcomas and plays an important role in growth of osteosarcoma cells by deregulation of both the pRb and p53 cell growth control pathways. Based on previously published studies, p16 protein negative expression on IHC is a predictive biomarker to poor pathologic response to neoadjuvant chemotherapy and is associated with a worse prognosis. p16 expression is correlated to the tumor biology and is not influenced by chemotherapy treatment. Thus, given the paucity of Indian data and lack of prospective studies, we aimed to investigate the role of P16 protein expression as a predictive biomarker in osteosarcoma. Aim: To investigate the relationship of p16 expression in pretreatment osteosarcoma tumors to pathologic necrotic response after neoadjuvant chemotherapy in a prospective pilot study. Inclusion criteria: Histologically proven cases of newly diagnosed osteosarcoma planned for neoadjuvant chemotherapy. Exclusion criteria: 1. Metastatic and relapsed osteosarcoma; 2. Upfront operated cases of osteosarcoma; 3. Prior therapy. Study procedure: Immuno-histochemistry for p16 will be conducted in core biopsy samples upfront before starting neoadjuvant chemotherapy in newly diagnosed case of osteosarcoma tumor cell necrosis rate will be calculated after neoadjuvant chemotherapy on surgical specimen. The grade of tumour cell necrosis rate will be classified using the Huvos necrosis grading system P16 correlation with good response to chemotherapy in terms of tumour necrosis will be evaluated. The author.
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