Won et al. BMC Cancer 2010, 10:564 http://www.biomedcentral.com/1471-2407/10/564 cyclin D1 and anti-apoptosis protein, survivin, has been investigated in malignancies [10-13]. Kim et al. reported the expression and clinical significance of cell cycle regula- tory proteins in biliary tract cancer. They presented that cyclin D1 overexpression was more common in extrahepa- tic bile duct cancer than in GB cancer. In univariate analy- sis, cyclin D1 and p53 showed no prognostic impact on survival in biliary tract cancer [10]. Jarnagin et al. also pre- sented that biliary tract cancers differentially expressed cell cycle regulatory protein based on tumor location and morphology. According to their results, cyclin D1 overex- pression varied based on anatomic site, and it was less common in GB cancer. However, there was no difference in p53 overexpression according to anatomic site, and prognostic roles were not identified for cyclin D1 and p53 [11]. In our study, there was no difference in p53 and cyclin D1 overexpression based on anatomic site, and also they were no prognostic impact on survival in BDC and GB cancer, respectively. Survivin is a member of the inhi- bitor of apoptosis family that regulates cell division and suppresses apoptosis [8]. In previous reports, survivin overexpression was correlated with poor prognosis in some gastrointestinal malignancies such as gastric cancer and pancreatic cancer [8]. Javel et al. also reported that nuclear survivin expression was associated with poor prog- nosis in cholangiocarcinoma [14]. However, in our study, there was no difference in survivin expression according to anatomic site, and no correlation between survivin expression and prognosis in biliary tract cancer. Additionally, we examined the expression of TP and ERCC1 associated with the response to 5-FU and cispla- tin chemotherapy [15]. No significant differences were found in the expression of p53, cyclin D1, survivin, and ERCC1 between GB cancer and BDC. However, TP expression was significantly higher in GB cancer than in BDC. This result can explain why these two cancers have shown different response rates to capecitabine combina- tion chemotherapy in many clinical trials. TP represents the rate-limiting enzyme in the activation of 5’-DFUR and capecitabine. The 5-FU prodrug capecitabine is metabolized to 5-FU through a three-step enzymatic con- version. In the final step, 5’-DFUR is metabolized to the active form 5-FU by TP. Therefore, the sensitivity of tumor cells to capecitabine might be enhanced by increasing TP expression [3,16]. Actually, Kim et al. pre- sented results from a phase II study of capecitabine plus cisplatin as a first-line chemotherapy for advanced biliary cancer. According to their results, GB cancer appeared to respond better to capecitabine and cisplatin treatment than BDC (32% vs 13%) [17,18]. In another phase II study with capecitabine and oxaliplatin, Nehls et al. reported that the response rates for GB, extrahepatic, and intrahepatic cholangiocarcinoma were 30%, 25%, and 0%, respectively [19]. In this study, we cannot access the Page 7 of 8 clinical correlations between TP expression and response to capecitabine and survival, because capecitabine for biliary tract cancers was unavailable in Korea during 1994-2003. However, based on our results, correlative studies will be warranted. Also, in the future, randomized trials of biliary tract cancer should be performed based on stratification by anatomical site. Meanwhile, correla- tion studies with clinico-pathological variables revealed a significant association between positive TP and p53 stain- ing with an advanced stage of the disease. These results are in accordance with previous studies, and the pro- angiogenic activity of TP can explain the more aggressive behavior of TP-expressing tumors [3]. Conclusions In summary, there were some differences in clinico- pathological characteristics, prognostic factors, and recurrence patterns between GB cancer and BDC. There- fore, these differences should be considered when plan- ning clinical trials and treatments. Additionally, further studies may be required to evaluate whether TP expres- sion can be used as a predictive marker for the clinical response to capecitabine chemotherapy in GB cancer. Acknowledgements We thank Dr. Jung Seok Yu for contribution in editing the figures. No specific funding was received. Author details 1Division of Medical Oncology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, Kyonggi-do, Korea. 2Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary’s Hospital, Seoul, Korea. 3Department of Hospital Pathology, Seoul St. Mary’s Hospital, Seoul, Korea. 4Department of Surgery, Seoul St. Mary’s Hospital, Seoul, Korea. 5Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, Seoul, Korea. Authors’ contributions HSW drafted the manuscript. HSW, MAL, DGK, YKY, THH and ISL collected the data and followed the patients. ESC evaluated H&E stained and immunostained slides. DGK, YKY, and THH provided the clinical specimens for this study and clinical perspective. MAL designed the study and helped with the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 30 April 2010 Accepted: 19 October 2010 Published: 19 October 2010 References 1. de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM: Biliary tract cancers. N Engl J Med 1999, 341(18):1368-1378. 2. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010, 362(14):1273-1281. 3. Andreetta C, Puppin C, Minisini A, Valent F, Pegolo E, Damante G, et al: Thymidine phosphorylase expression and benefit from capecitabine in patients with advanced breast cancer. Ann Oncol 2009, 20(2):265-271. 4. Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, et al: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006, 355(10):983-991.