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Expression of X-linked Inhibitor of Apoptosis as a Novel Prognostic Marker in Radically Resected Non-Small Cell Lung Cancer Patients¹

Departments of Medical Oncology [C. G. F., S. W. S., I. L., F. A. E. K., H. M. P., G. G.], Pathology [P. v. d. V.], and Pulmunology [E. F. S.], Academic Hospital Vrije Universiteit Amsterdam, 1081 HV Amsterdam, and Comprehensive Cancer Center Amsterdam [H. v. T.], the Netherlands

Purpose: To assess the pattern of expression and the prognostic value of the inhibitor of apoptosis family member X-linked inhibitor of apoptosis (XIAP; MIHA/ILP-a) in radically resected non-small cell lung cancer patients.

Experimental Design: The expression of XIAP and its relationship with overall survival was analyzed by immunohistochemistry on tumors from 144 patients with early-stage non-small cell lung cancer. In addition, the apoptotic and mitotic index, Ki-67, p53, and bcl-2 levels were also assessed.

Results: XIAP expression was specific for tumor cells, and the pattern was cytoplasmic. The median expression of XIAP was 20%, and when this value was used as a cutoff point for statistical analyses, 63 of the samples were considered high XIAP-expressing and 81 low XIAP-expressing. Surprisingly, high XIAP-expressing patients had a longer overall survival than the group expressing lower levels (60 versus 24 months of median survival; log rank, P = 0.01). The positive impact of XIAP expression on survival was confirmed by multivariate analysis (P = 0.026). Although no correlation was observed between XIAP expression and the apoptotic index, a significant inverse correlation was observed between XIAP, Ki-67 (P = 0.006), and mitotic index (P = 0.04).

Conclusions: The unexpected inverse correlation of XIAP with proliferation markers and the absence of correlation with apoptotic index, coupled with its role as an independent positive prognostic factor for survival in radically resected NSCLC patients imply a more complex role for XIAP in tumor biology than anticipated by in vitro data.

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