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Nuclear expression of survivin is associated with improved survival in metastatic ovarian carcinoma
Author(s) -
Kleinberg Lilach,
Flørenes Vivi Ann,
Silins Ilvars,
Haug Kristiane,
Trope Claes G.,
Nesland Jahn M.,
Davidson Ben
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22426
Subject(s) - survivin , xiap , inhibitor of apoptosis , immunohistochemistry , medicine , cancer research , ovarian cancer , pathology , cancer , apoptosis , oncology , biology , programmed cell death , biochemistry , caspase
BACKGROUND. Inhibitor of apoptosis proteins (IAPs) mediate cancer cell survival and chemoresistance. The expression of XIAP, Survivin, and Livin in ovarian carcinoma was analyzed. METHODS. Effusions (106) were analyzed for XIAP, Survivin, and Livin expression using immunoblotting. Effusions (220), corresponding primary tumors (60), and solid metastases (103) were further immunohistochemically analyzed for XIAP and Survivin expression. The results were analyzed for association with anatomic site, clinicopathologic parameters, and survival. RESULTS. Immunoblotting showed frequent expression of XIAP and Survivin, and no expression of Livin. Immunohistochemistry showed cytoplasmic XIAP expression in 208 of 220 (94%) effusions, 50 of 60 (83%) primary tumors, and 87 of 103 (84%) solid metastases, with a significantly higher staining extent in effusions ( P < .001). Cytoplasmic Survivin was found in 194 of 220 (88%) effusions, 55 of 60 (92%) primary tumors, and 102 of 103 (99%) solid metastases, with a significantly higher cytoplasmic staining extent in solid metastases ( P = .018 and P = .006 compared with primary tumors and effusions, respectively). Nuclear Survivin was expressed in 159 of 220 (72%) effusions, 54 of 60 (90%) primary carcinomas, and 96 of 103 (93%) solid metastases ( P > .05). For patients with prechemotherapy effusions, higher nuclear Survivin expression correlated with better progression‐free ( P = .0003) and overall ( P = .002) survival in univariate survival analysis. Nuclear Survivin expression was found to be an independent predictor of progression‐free survival ( P = .004). CONCLUSIONS. XIAP and Survivin, but not Livin, are frequently expressed in ovarian carcinoma. XIAP and cytoplasmic Survivin are up‐regulated in effusions and solid metastases, respectively, possibly mediating survival at these sites. Nuclear Survivin expression predicts better outcome in prechemotherapy patients. Cancer 2007. © 2006 American Cancer Society.