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Prognostic Significance of the Immunohistochemical Staining of Cleaved Caspase-3, an Activated Form of Caspase-3, in Gliomas

Authors' Affiliations: Departments of ¹ Pathology, ² Neurosurgery, and ³ Preventive Medicine, Shinshu University School of Medicine, Matsumoto, Japan

Requests for reprints: Junya Masumoto, Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. Phone: 81-263-37-3395; Fax: 81-263-37-2581; E-mail: masumoto{at}sch.md.shinshu-u.ac.jp.

Purpose: Gliomas are common tumors of the central nervous system, and the majority of patients with gliomas have a poor prognosis. The prediction of prognosis is very important in selecting treatment. In the present study, we retrospectively examined the immunohistochemical staining of cleaved caspase-3 (CC3), an activated form of caspase-3 that acts as a lethal protease at the most distal stage of the apoptosis pathway, in gliomas, and the correlation between the prognosis of patients and caspase-3 activation to find useful prognostic indicators.

Experimental Design: Immunohistochemical staining of CC3 was done in 65 patients with gliomas. The percentage of CC3 staining-positive cells was defined as the CC3 immunoreactivity score (IRS). Survival analysis between CC3 IRS of glioma patients and survival time was carried out using the Kaplan-Meier method with the log-rank test and the Cox proportional hazards regression model.

Results: CC3 IRS was statistically analyzed to designate the best provisional cutoff point, and when detected in >10% of glioma cells, it was considered positive. The Kaplan-Meier method with the log-rank test revealed that patients with CC3 IRS-positive tumors had significantly greater survival than those with CC3 IRS-negative tumors among three grades, 2, 3, and 4 (P = 0.0061), and within grade 3 of anaplastic astrocytoma (P = 0.0458). After adjustment for known clinical prognostic factors, such as age, WHO grade, and performance status, the hazard ratio for CC3 IRS-positive was 0.39 with 95% confidence interval between 0.19 and 0.85 (P = 0.0187). Within high grades, including grades 3 and 4, the hazard ratio was 0.40 with 95% confidence interval between 0.20 and 0.86 (P = 0.0192).

Conclusions: CC3 IRS could be useful as a good prognostic indicator for glioma patients.

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