Abstract
BackgroundThe polycomb transcription factor Yin Yang 1 (YY1) overexpression can be causally implicated in experimental tumor growth and metastasization. To date, there is no clinical evidence of YY1 involvement in outcome of patients with osteosarcoma. Prognosis of osteosarcoma is still severe and only few patients survive beyond five years. We performed a prospective immunohistochemistry analysis to correlate YY1 immunostaining with metastatic development and survival in a selected homogeneous group of patients with osteosarcoma.MethodsWe studied 41 patients suffering from osteosarcoma (stage II-IVa). Multivariate analysis was performed using Cox proportional hazard regression to evaluate the correlation between YY1 expression and both metastasis development and mortality.ResultsYY1 protein is not usually present in normal bone; in contrast, a high number of patients (61%) showed a high score of YY1 positive cells (51-100%) and 39% had a low score (10-50% positive cells). No statistical difference was found in histology, anatomic sites, or response to chemotherapy between the two degrees of YY1 expression. Cox regression analysis demonstrated that the highest score of YY1 expression was predictive of both low metastasis-free survival (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039) and poor overall survival (HR = 8.353, 95%CI = 1.863-37.451 p = 0.006) regardless of the effects of covariates such as age, gender, histology and chemonecrosis.ConclusionOverexpression of YY1 in primary site of osteosarcoma is associated with the occurrence of metastasis and poor clinical outcome.
Highlights
The polycomb transcription factor Yin Yang 1 (YY1) overexpression can be causally implicated in experimental tumor growth and metastasization
YY1 overexpression in osteosarcoma tissues Immunohistochemistry revealed that all normal bone tissues analyzed (n = 10) were almost negative to YY1
Multivariate Cox regression analysis revealed that a high level of YY1 expression was predictive of poor metastasis-free survival (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039) (Table 3 and Figure 2)
Summary
The polycomb transcription factor Yin Yang 1 (YY1) overexpression can be causally implicated in experimental tumor growth and metastasization. Osteosarcoma is the most common primary malignant bone tumor in adolescents and children [1]. Despite recent advances in chemotherapy, the 5-year event-free survival and overall survival rates, closely linked to grade of osteosarcoma, are around 50-60%. This is due to the development of resistance to multiple types of chemotherapy and radiotherapy [2,3,4]. There is no evidence of correlation between YY1 overexpression and clinical outcome in osteosarcoma patients. We designed a prospective study to analyze whether YY1 expression in the primary tumor of osteosarcoma patients could predict metastasis-free and overall survival
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