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Large differences in terms of incidence and mortality due to gallbladder cancer (GBC) have been reported worldwide. Moreover, it seems that GBC has unique characteristics in South America. We surveyed the literature looking for information about the epidemiology, basic and translational research, and clinical trials performed in South America in order to critically analyze the magnitude of this health problem in the region. Compared to other geographic areas, age-standardized mortality rates (ASMR) for GBC in women are very high, particularly in many western areas of South America. Genetic, as well as dietary and environmental factors likely contribute to the pathogenesis of this disease in the area. Compared to other regions the profile of abnormalities of key genes such as KRAS and TP53 in GBC seems to slightly differ in South America, while the clinical behavior appears to be similar with a median overall survival (OS) of 6.5 to 8 months in advanced GBC. In contrast to Europe and USA, prophylactic cholecystectomy is a common practice in western areas of South America. GBC particularly affects women in South America, and represents a significant public health problem. It appears to have peculiarities that pose an urgent need for additional research aimed to discover risk factors, molecular events associated with its development and new treatment options for this lethal disease.

e14521 Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7.

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