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SPARC tied to reduced survival in head and neck cancer

Last Updated: 2005-02-21 6:22:16 -0400 (Reuters Health)

NEW YORK (Reuters Health) - SPARC, also known as osteonectin, is an independent marker of poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC), investigators from Australia report in the February 20th issue of the International Journal of Cancer.

"Of all human cancer, HNSCC is the most distressing, affecting the basic survival functions of swallowing and breathing," Dr. David Chin from the University of Queensland in Brisbane told Reuters Health.

Surgical resection often yields the best outcome but is disfiguring, requires extensive reconstructive surgery, and may be of little benefit to patients with short disease-free intervals.

"If we could determine preoperatively who we should operate on and those that would benefit from conservative or organ/function preserving surgery," he added, "this would spare them from suffering twice -- first the cancer and then a major reconstructive surgery."

To identify markers of poor prognosis, Dr. Chin's team compared the expression of 13,000 genes in malignant and normal oral mucosa in 7 patients with HNSCC. A total of 1,260 candidate genes displayed statistically significant differences in expression between normal and cancerous tissue.

SPARC was elevated consistently in matched cDNA microarray analysis in the transition from normal mucosa to tumor tissue in the seven patients studied.

The researchers then analyzed SPARC and two other top candidate genes in 62 HNSCC patients. In multivariate survival analysis, SPARC emerged as a "powerful independent prognostic marker" for short disease-free interval and poor overall survival.

The association between SPARC/osteonectin and reduced disease-free interval and overall survival became even more significant (p<0.001) when combined with two other extracellular matrix proteins, PAI-1 and uPA. This combination also outperformed traditional prognostic markers such as nodal involvement and tumor size.

"We believe," Dr. Chin concluded, "that these markers can accurately predict from routine outpatient diagnostic work-up those patients that will have a good prognosis, early recurrence, or poor prognosis, regardless of treatment modality."

Int J Cancer 2005;113:789-797.

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