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Annals of Oncology Advance Access published online on October 29, 2009
Annals of Oncology, doi:10.1093/annonc/mdp459
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study

G. Lahat1,2, D. Tuvin1,2, C. Wei3, W. L. Wang4, R. E. Pollock1,2, D. A. Anaya1, B. N. Bekele3, L. Corely4, A. J. Lazar2,4, P. W. Pisters1 and D. Lev2,5,*

1 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2 Department of Sarcoma Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
5 Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

* Correspondence to: Dr D. Lev, Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 8515 Fannin Street, Unit 1104, Houston, TX 77030, USA. Tel: +1-713-792-0841; Fax: +1-713-563-1185; E-mail: dlev{at}mdanderson.org

Background: Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. We sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS).

Materials and methods: A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence.

Results: Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance.

Conclusions: Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.

matrix metalloproteinase, molecular markers, outcome, prognostic factors, soft tissue sarcoma

Received for publication August 7, 2009. Accepted for publication August 13, 2009.


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