Won et al. BMC Cancer 2010, 10:564 http://www.biomedcentral.com/1471-2407/10/564 Table 4 Univariate survival analysis according to clinico-pathological variables All patients Median Survival GB cancer Median Survival Bile duct cancer Median Survival 22 24 99 18 13 27 19 40 18 31 18 32 83 22 12 5 20 30 25 22 27 22 22 21 18 27 p 0.939 0.001 0.022 0.001 0.011 0.001 0.001 0.210 0.890 0.339 0.463 0.241 . 17 12 27 16 30 16 30 38 10 . 20 9 5 19 30 20 21 20 21 22 19 21 20 p 0.001 0.029 0.029 0.047 0.001 0.001 0.409 0.943 0.995 0.625 0.903 Variable Anatomic location Well differentiated Vascular invasion Perineural invasion Lymphatic invasion Lymph node metastasis Stage P53 Cyclin D1 Survivin TP ERCC1 GB Bile duct Yes No Positive Negative Positive Negative Positive Negative Positive Negative 1 2 3 4 Positive Negative Positve Negative Positive Negative Positive Negative Positive Negative GB, gallbladder; TP, thymidine phosphorylase; ERCC1, excision repair cross complementing protein 1. GB cancer was more frequent in women, and BDC was more common in men. These sex differences are prob- ably related to the higher incidence of gallstones in women and of primary sclerosing cholangitis in men, which are known risk factors for GB cancer and BDC, respectively [1]. Another anatomical site-related differ- ence was the frequency of perineural invasion. Peri- neural invasion is a distinct pathological entity that can be observed in the absence of lymphatic and vascular invasion [9]. Although the pathogenesis and clinical sig- nificance of perineural invasion remain unclear, it is considered an under-recognized route of metastatic spread. For some malignancies including head and neck, pancreas, colorectum, and prostate, perineural invasion has been associated with a lower 5 year survival rate and a more advanced disease stage [9]. In our study, perineural invasion was observed more frequently in BDC than in GB cancer. Additionally, univariate analysis revealed that perineural invasion was one of the prog- nostic factors in biliary tract cancer. Meanwhile, some differences were found in recurrence patterns and prog- nostic factors between GB cancer and BDC. BDC had higher local recurrence than GB cancer, while recur- rence as a distant metastasis was more common in GB cancer. These differences should be considered to deter- mine adjuvant therapy after curative resection. In uni- variate analysis, differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in GB cancer than in BDC. Also, in multivariate analysis, differentiation and TNM stage showed a prognostic impact on survival in biliary tract cancer. Taken together, GB cancer and BDC are thought to be separate diseases with differences in pathogenesis influencing clinical behavior. We assessed the expression of p53, cyclin D1 and survi- vin, to compare the differences in molecular changes asso- ciated with the prognosis between BDC and GB cancer. Apoptosis and cell cycle control are processes required for the regulation of cellular homeostasis. Chronic imbalance between apoptosis and cell proliferation is the first step of carcinogenesis in all tumors. Therefore, prognostic signifi- cance of cell cycle regulatory protein such as p53 and 85 19 13 26 19 . 18 31 21 30 36 26 13 8 24 35 25 32 58 25 22 32 14 33 Page 6 of 8 p 0.001 0.261 0.005 0.080 0.058 0.069 0.374 0.962 0.267 0.194 0.073