4092 Background: Survivin is a unique anti apoptotic protein expressed in many human cancers. It is absent in non-proliferating adult tissues. Its expression and prognostic value in biliary tumors is yet to be elucidated. Methods: Twenty-four consecutive surgical cases of cholangiocarcinoma treated from 1996–2002 at Roswell Park Cancer Institute were studied. Immunohistochemistry was performed on paraffin embedded blocks using mouse monoclonal IgG2a antibody to survivin (Santa Cruz Biotechnology). DAKO high pressure antigen retrieval and mouse envision plus detection systems were used to detect survivin expression. Two pathologists (DT, CL) independently examined survivin expression and scored (0, 1+, 2+, 3+), based on presence and intensity of immunoreactivity in nucleus and cytoplasm. Clinical data were obtained in accordance with IRB approved protocol. Results: Median patient (pt) age was 68 (range 40 to 77). Sixteen pts were female, and 8 male. SEER staging was local in 2, regional in 15 and distant in 7 pts. Treatments included chemotherapy (2 pts), surgery (10), combined modality (10) or no therapy (2). Strong cytoplasmic survivin expression (3+) was seen in 6 cases and strong nuclear survivin (3+) in 4. One case had strong co-expression at both locations. There was no statistical correlation between expression of either cytoplasmic or nuclear survivin with sex, SEER staging or tumor grade. Statistically, cytoplasmic survivin expression did not have prognostic significance. However, 4 pts with strong nuclear survivin had a median survival of 11 months, significantly less than those with weak nuclear survivin expression (20 months, p=0.033). Multivariate analysis using the Cox- proportional hazards model identified the following 4 as best predictors of patient mortality: nuclear survivin (P=0.022), presence of metastasis (P=0.025), age (P=0.019), and use of combined modality therapy (P=0.006). Estimated hazard ratios (HR) suggested pts likely to survive longer were weak nuclear survivin expressers (HR = 3.1) and had non- metastatic disease (HR = 1.5). Conclusions: Nuclear survivin expression in cholangiocarcinoma may identify those with a poor prognosis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Eli Lilly; Genentech; MGI Phama Eli Lily; Pfizer; Roche