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Open Access Research article

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

Filomena de Nigris16*, Licciana Zanella2, Francesco Cacciatore3, Anna De Chiara4, Flavio Fazioli5, Gennaro Chiappetta4, Gaetano Apice5, Teresa Infante6, Mario Monaco4, Raffaele Rossiello8, Gaetano De Rosa7, Marco Alberghini2 and Claudio Napoli16

Author Affiliations

1 Department of General Pathology, Division of Clinical Pathology and U.O.C. Immunohematology, Second University of Naples, 80138 Naples, Italy

2 Department of Surgical Pathology, Rizzoli Orthopedic Institute, 40136 Bologna, Italy

3 Salvatore Maugeri Foundation, Telese-Terme, 82037 Benevento, Italy

4 Division of Pathology National Cancer Institute, Pascale Foundation, 80131 Naples, Italy

5 Division of Thoracic Surgery, Sarcoma Team National Cancer Institute, Pascale Foundation, 80131 Naples, Italy

6 SDN Foundation, Institute of Diagnostic and Nuclear Development, via E. Gianturco 113, 80143 Naples, Italy

7 Department of Human Pathology, Federico II University of Naples, 80131 Naples, Italy

8 Department of Human Pathology, Second University of Medicine, 80138 Naples, Italy

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BMC Cancer 2011, 11:472  doi:10.1186/1471-2407-11-472

Published: 2 November 2011

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.