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To the Editor: Dr Kim and colleagues¹ found elevated serum osteopontin levels in patients with ovarian carcinoma. While the authors' approach has high sensitivity, the nonspecific nature of osteopontin expression in many diseases limits the potential clinical application of serum osteopontin as a unique biomarker for ovarian cancer.

Test specificity is central to any biomarker or screening program. Osteopontin may be expressed in many inflammatory and noninflammatory diseases including cancers of varied tissue origin.^2-3 Although a variety of cell types express osteopontin, macrophages are a major source.² Even in carcinoma, there is evidence that infiltrating macrophages rather than tumor cells are the principal source of osteopontin.³ Prior investigations have shown very high levels of osteopontin in hemodialysis patients with arterial atherosclerosis and in patients with gram-negative sepsis.⁴ These studies suggest that assays of total serum osteopontin alone will lack sufficient specificity to be a clinically applicable cancer biomarker.

In contrast . . . [Full Text of this Article]

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