Expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase in human breast carcinoma cells and tissues.
BACKGROUND
The therapeutic effects of oral capecitabine are proposed to be determined by the equilibrium of two intratumoral metabolizing enzymes, namely thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). The present study aims to evaluate this hypothesis by in vivo experiments and immunohistochemical analysis in 31 cases of human breast carcinoma.


METHODS
The effects of capecitabine on two breast carcinoma cell lines were evaluated by the status of both cell proliferation and apoptosis and mRNA levels of TP and DPD were also determined. TP and DPD status was determined by immunohistochemistry in 31 cases of breast carcinoma tissues and the results were compared with their clinicopathological parameters.


RESULTS
The therapeutic efficacy of capecitabine in two cell lines was not related to the levels of TP and DPD mRNA expression. No statistically significant association was detected between the status of these enzymes and the clinicopathological factors.


CONCLUSIONS
In vitro study demonstrated that capecitabine was effective against the BT-483 and MB-MDA-231 breast carcinoma cell lines used but the significance of the status of intratumoral TP and DPD in determining its therapeutic efficacy needs further studies.
Loo
Wings T Y
WT
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. tyloo@hku.hk
Chow
Louis W C
LW
Suzuki
Takashi
T
Ono
Katsuhiko
K
Ishida
Takanori
T
Hirakawa
Hisashi
H
Ohuchi
Noriaki
N
Sasano
Hironobu
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D000069287:Capecitabine; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D003841:Deoxycytidine; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; D005472:Fluorouracil