Expression of P16 in Osteosarcoma as Predictive Neo-Adjuvant Therapy Factor.
Dariusz Borys, Robert J Canter, Robert M Tamurian, Benjamin Hoch, Brian Murphy, John Bishop, Andrew E Horvai. University of California Davis, Sacramento; UC Davis, Sacramento, CA; University of Washington, Seattle; UCSF, San Francisco, CA; UC Davis, Davis, CA
Background: Osteosarcoma is a common malignant primary tumor of bone affecting adolescent and young adults. Osteosarcomas are high grade sarcomas with aggressive behavior. There are few if any molecular markers to predict behavior and prognosis of osteosarcoma. The objective of this study is to investigate expression of p16 in correlation with neo-adjuvant chemotherapy response in osteosarcoma.
Design: A tissue micro array was created using paraffin embedded samples from 40 pretreatment osteosarcoma cases from two institutions UC Davis and UCSF. Immunohistochemistry was performed with commercially available p16 monoclonal mouse antibody (mtm laboratories AG, Germany). Expression of p16 was defined as cytoplasmic staining in at least 30% of cells. Percent tumor necrosis was measured in post-chemotherapy resection specimens with good response set at >90% necrosis. Data were also abstracted on age, sex, tumor site, and histologic subtype. Univariate and multivariate analysis was performed.
Results: Patients age ranged from 9 to 75 years (mean 20). Most common locations were tibia and femur. 21 patients were female and 19 male. The clinical and p16 results are summarized in [table 1]. p16 expression correlated positively with median percent necrosis and fraction of cases with good chemotherapy response (p=0.004 and 0.003, respectively). On multivariate analysis, p16 expression was independently associated with chemotherapy response after controlling for other factors.
|Characteristic||p16 Positive (N=25)||p16 Negative (N=15)||P Value|
|Median Age, IQR||15,12-21||17, 13-26||0.51|
|Sex: Male/Female||15 (60%)/10 (40%)||4 (27%)/11 (73%)||0.06|
|Median Percent Necrosis/ Range||95/ 90-99||40/ 10-90||0.004|
|Pathologic "good" response (>90%)* : Yes/ No||18 (78%)/ 5 (22%)||4 (27%)/ 11 (73%)||0.003|