Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer.
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.
Division of Medical Oncology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, Seoul, Korea.
Hye Sung
HS
Won
Myung Ah
MA
Lee
Eun-Seon
ES
Chung
Dong-Goo
DG
Kim
Young Kyoung
YK
You
Tae Ho
TH
Hong
In-Seok
IS
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000201:enzymology*; D019938:Cyclin D1 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004720:Endonucleases / Q000096:biosynthesis; D005260:Female; D005706:Gallbladder Neoplasms / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D012737:Sex Factors; D000077022:Survivin; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D013939:Thymidine Phosphorylase; C071447:ERCC1 protein, human; D004720:Endonucleases