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Bone Sialoprotein Is Predictive of Bone Metastases in Resectable Non–Small-Cell Lung Cancer: A Retrospective Case-Control Study

Mauro Papotti, Thea Kalebic, Marco Volante, Luigi Chiusa, Elisa Bacillo, Susanna Cappia, Paolo Lausi, Silvia Novello, Piero Borasio, Giorgio V. Scagliotti

From the Department of Clinical & Biological Sciences, and Department of Biomedical Sciences & Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy; and Novartis Oncology, East Hanover, NJ

Address reprint requests to Giorgio V. Scagliotti, MD, PhD, Department of Clinical & Biological Sciences, University of Turin, San Luigi Hospital, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; e-mail: giorgio.scagliotti{at}unito.it

PURPOSE: Bone metastases (BM) in non–small-cell lung cancer (NSCLC) may be detected at diagnosis or during the course of the disease, and are associated with a worse prognosis. Currently, there are no predictive or diagnostic markers to identify high-risk patients for metastatic bone dissemination.

PATIENTS AND METHODS: Thirty patients with resected NSCLC who subsequently developed BM were matched for clinicopathologic parameters to 30 control patients with resected NSCLC without any metastases and 26 patients with resected NSCLC and non-BM lesions. Primary tumors were investigated by immunohistochemistry for 10 markers involved in bone resorption or development of metastases. Differences among groups were estimated by ² test, whereas the prognostic impact of clinicopathologic parameters and marker expression was evaluated by univariate (Wilcoxon and Mantel-Cox tests) and multivariate (Cox proportional hazards regression model) analyses.

RESULTS: The presence of bone sialoprotein (BSP) was strongly associated with bone dissemination (P < .001) and, independently, with worse outcome (P = .02, Mantel-Cox test), as defined by overall survival. To evaluate BSP protein expression in nonselected NSCLC, a series of 120 consecutive resected lung carcinomas was added to the study, and BSP prevalence reached 40%. No other markers showed a statistically significant difference among the three groups or demonstrated a prognostic impact, in terms of both overall survival and time interval to metastases.

CONCLUSION: BSP protein expression in the primary resected NSCLC is strongly associated with BM progression and could be useful in identifying high-risk patients who could benefit from novel modalities of surveillance and preventive treatment.

Supported by an unrestricted research grant from Novartis Pharma (New York, NY)

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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