Nuclear expression of survivin is associated with improved survival in metastatic ovarian carcinoma.
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.
Kleinberg
Lilach
L
Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
Flørenes
Vivi Ann
VA
Silins
Ilvars
I
Haug
Kristiane
K
Trope
Claes G
CG
Nesland
Jahn M
JM
Davidson
Ben
B
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C107489:BIRC5 protein, human; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human