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Carbonic Anhydrase IX as a Marker for Poor Prognosis in Soft Tissue Sarcoma

¹ Ontario Cancer Institute/Princess Margaret Hospital, ² Mount Sinai Hospital, and Departments of ³ Medical Biophysics, ⁴ Radiation Oncology, ⁵ Medicine, ⁶ Pathology, and ⁷ Surgery, University of Toronto, Toronto, Ontario, Canada

Purpose: Hypoxia is associated with malignant progression and poor outcome in several human tumors, including soft tissue sarcoma. Recent studies have suggested that carbonic anhydrase (CA) IX is an intrinsic marker of hypoxia, and that CA IX correlates with poor prognosis in several types of carcinoma. The aim of this study was to quantify the extent of CA IX expression and to investigate whether CA IX is a marker for poor prognosis in soft tissue sarcoma patients at high risk of developing metastasis.

Experimental Design: Archival paraffin-embedded blocks were retrieved from 47 patients with deep, large, high-grade soft tissue sarcoma. Sections from two separate and representative tumor areas were immunostained for CA IX, and the CA IX-positive area fraction was quantified by image analysis, excluding areas of normal stroma and necrosis that were identified from serial H&E-stained sections. Patients were then subject to survival analysis.

Results: CA IX-positive area fractions of viable tumor tissue varied significantly between tumors (range, 0–0.23; median, 0.004), with positive membranous CA IX staining in 66% (31 of 47) of the tumors. Patients with CA IX-positive tumors had a significantly lower disease-specific and overall survival than patients with CA IX-negative tumors (P = 0.033 and P = 0.044, respectively).

Conclusions: These data suggest that CA IX, a potential intrinsic marker of hypoxia, predicts for poor prognosis in patients with deep, large, high-grade soft tissue sarcoma. Larger studies are required to determine whether CA IX has independent prognostic value in this group of tumors.

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