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. 2011 Nov 2:11:472.
doi: 10.1186/1471-2407-11-472.

YY1 overexpression is associated with poor prognosis and metastasis-free survival in patients suffering osteosarcoma

Filomena de Nigris  1 , Licciana Zanella, Francesco Cacciatore, Anna De Chiara, Flavio Fazioli, Gennaro Chiappetta, Gaetano Apice, Teresa Infante, Mario Monaco, Raffaele Rossiello, Gaetano De Rosa, Marco Alberghini, Claudio Napoli
Affiliations

YY1 overexpression is associated with poor prognosis and metastasis-free survival in patients suffering osteosarcoma

Filomena de Nigris et al. BMC Cancer. .

Abstract

Background: The 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.

Methods: We 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.

Results: YY1 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.

Conclusion: Overexpression of YY1 in primary site of osteosarcoma is associated with the occurrence of metastasis and poor clinical outcome.

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Figures

Figure 1
Figure 1
Two comparative examples of YY1 expression in osteosarcomas. A, osteobastic osteosarcoma specimen with 2 as score of immunoreactivity to YY1 at lower magnification (20x); B, the same specimen as in A at higher magnification (100x); C, osteoblastic osteosarcoma specimen with 4 as score of immunoreactivity to YY1 (20x); D, the same osteoblastic osteosarcoma specimen as in C at higher magnification (100x). YY1 protein was localized in nuclei of the cells.
Figure 2
Figure 2
Cox regression of cumulative metastasis-free survival rate. The graph shows the cumulative metastasis-free survival of high grade osteosarcoma patients using Cox multivariate analysis. The data indicates that high score of YY1 is associated with higher probability of developing metastasis during the follow up (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039). HR= hazard ratio; CI=confidence interval.
Figure 3
Figure 3
Cox regression of cumulative survival rate of all patients. The graph shows the cumulative overall survival rate of high grade osteosarcoma patients (n = 41) using Cox multivariate analysis. The data indicates that higher score of YY1 (3-4) predicts mortality during the follow up. (HR = 8.353, 95%CI = 1.863-37.451, p = 0.006) HR= hazard ratio; CI=confidence interval.
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