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BMC Cancer

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Open Access 01-12-2010 | Research article

Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer

Authors: Hye Sung Won, Myung Ah Lee, Eun-Seon Chung, Dong-Goo Kim, Young Kyoung You, Tae Ho Hong, In-Seok Lee

Published in: BMC Cancer | Issue 1/2010

Abstract

Background

Biliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1.

Methods

One hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry.

Results

With respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. 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 gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers.

Conclusions

We concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by gallbladder cancer results in a higher response rate to capecitabine by gallbladder cancer than bile duct cancer.

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de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM: Biliary tract cancers. N Engl J Med. 1999, 341 (18): 1368-1378. 10.1056/NEJM199910283411807.CrossRefPubMed

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. 10.1056/NEJMoa0908721.CrossRefPubMed

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. 10.1093/annonc/mdn592.CrossRefPubMed

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. 10.1056/NEJMoa060570.CrossRefPubMed

Andino L, Cagle PT, Murer B, Lu L, Popper HH, Galateau-Salle F, Sienko AE, Barrios R, Zander DS: Pleuropulmonary desmoid tumors: immunohistochemical comparison with solitary fibrous tumors and assessment of beta-catenin and cyclin D1 expression. Arch Pathol Lab Med. 2006, 130 (10): 1503-1509.PubMed

Saito H, Tsujitani S, Oka S, Kondo A, Ikeguchi M, Maeta M, Kaibara N: The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma. Br J Cancer. 1999, 81 (3): 484-489. 10.1038/sj.bjc.6690719.CrossRefPubMedPubMedCentral

Kim SH, Kwon HC, Oh SY, Lee DM, Lee S, Lee JH, Roh MS, Kim DC, Park KJ, Choi HJ, Kim HJ: Prognostic value of ERCC1, thymidylate synthase, and glutathione S-transferase pi for 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer. Am J Clin Oncol. 2009, 32 (1): 38-43. 10.1097/COC.0b013e31817be58e.CrossRefPubMed

Song KY, Jung CK, Park WS, Park CH: Expression of the antiapoptosis gene Survivin predicts poor prognosis of stage III gastric adenocarcinoma. Jpn J Clin Oncol. 2009, 39 (5): 290-296. 10.1093/jjco/hyp020.CrossRefPubMed

Liebig C, Ayala G, Wilks JA, Berger DH, Albo D: Perineural invasion in cancer: a review of the literature. Cancer. 2009, 115 (15): 3379-3391. 10.1002/cncr.24396.CrossRefPubMed

10.

Kim WB, Han HJ, Lee HJ, Park SS, Song TJ, Kim HK, et al: Expression and clinical significance of cell cycle regulatory proteins in gallbladder and extrahepatic bile duct cancer. Ann Surg Oncol. 2009, 16 (1): 23-34. 10.1245/s10434-008-0182-x.CrossRefPubMed

11.

Jarnagin WR, Klimstra DS, Hezel M, Gonen M, Fong Y, Roggin K, et al: Differential cell cycle-regulatory protein expression in biliary tract adenocarcinoma: correlation with anatomic site, pathologic variables, and clinical outcome. J Clin Oncol. 2006, 24 (7): 1152-1160. 10.1200/JCO.2005.04.6631.CrossRefPubMed

12.

Shen YC, Hu FC, Jeng YM, Chang YT, Lin ZZ, Chang MC, et al: Nuclear overexpression of mitotic regulatory proteins in biliary tract cancer: correlation with clinicopathologic features and patient survival. Cancer Epidemiol Biomarkers Prev. 2009, 18 (2): 417-423. 10.1158/1055-9965.EPI-08-0691.CrossRefPubMed

13.

Hui AM, Cui X, Makuuchi M, Li X, Shi YZ, Takayama T: Decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma. Hepatology. 1999, 30 (5): 1167-1173. 10.1002/hep.510300506.CrossRefPubMed

14.

Javle MM, Tan D, Yu J, LeVea CM, Li F, Kuvshinoff BW, Gibbs JF: Nuclear survivin expression predicts poor outcome in cholangiocarcinoma. Hepatogastroenterology. 2004, 51 (60): 1653-1657.PubMed

15.

Uchida K, Danenberg PV, Danenberg KD, Grem JL: Thymidylate synthase, dihydropyrimidine dehydrogenase, ERCC1, and thymidine phosphorylase gene expression in primary and metastatic gastrointestinal adenocarcinoma tissue in patients treated on a phase I trial of oxaliplatin and capecitabine. BMC Cancer. 2008, 8: 386-10.1186/1471-2407-8-386.CrossRefPubMedPubMedCentral

16.

Ahn MJ, Choi JH, Oh HS, Lee YY, Kim IS, Choi IY, et al: Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy. Cancer Res Treat. 2005, 37 (4): 216-222. 10.4143/crt.2005.37.4.216.CrossRefPubMedPubMedCentral

17.

Kim TW, Chang HM, Kang HJ, Lee JR, Ryu MH, Ahn JH, et al: Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer. Ann Oncol. 2003, 14 (7): 1115-1120. 10.1093/annonc/mdg281.CrossRefPubMed

18.

Hong YS, Lee J, Lee SC, Hwang IG, Choi SH, Heo JS, et al: Phase II study of capecitabine and cisplatin in previously untreated advanced biliary tract cancer. Cancer Chemother Pharmacol. 2007, 60 (3): 321-328. 10.1007/s00280-006-0380-9.CrossRefPubMed

19.

Nehls O, Oettle H, Hartmann JT, Hofheinz RD, Hass HG, Horger MS, et al: Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Br J Cancer. 2008, 98 (2): 309-315. 10.1038/sj.bjc.6604178.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/564/prepub

Title: Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
Authors: Hye Sung Won
Myung Ah Lee
Eun-Seon Chung
Dong-Goo Kim
Young Kyoung You
Tae Ho Hong
In-Seok Lee
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-10-564

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Abstract

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