DPD activity and immunohistochemical DPD expression in human breast cancer.
We investigated dihydropyrimidine dehydrogenase (DPD) activity and its expression in breast cancer cases, and evaluated the prognostic significance of DPD expression in invasive breast cancer. A total of 49 paired of breast cancer tissues and the adjacent normal breast tissues were evaluated in this study. DPD expression of 191 patients with invasive breast cancer was also evaluated immunohistochemically. DPD activity in breast cancer ranged from 13.4-360.0 pmol/mg/min (mean, 162.9 pmol/mg/min). DPD activity in breast cancer tissues was significantly (p<0.001) higher than in adjacent normal breast tissue. DPD activity was significantly higher in DPD expression-positive tumors than DPD expression-negative tumors. The level of DPD activity was correlated with DPD expression. Patients with DPD expression-positive tumors had a significantly (p<0.05) poorer prognosis in disease-free survival compared to those with DPD-negative tumors. When evaluated in patients treated with 5-FU or 5-FU derivatives, DPD expression was a significantly (p<0.05) poorer prognostic factor in disease-free and overall survival. Using a Cox proportional hazards model, nodal status, ER status, and DPD expression were independent prognostic factors for both disease-free and overall survival. In conclusion, DPD expression may function as a marker of DPD activity and may be a prognostic indicator for patients with breast cancer.
Horiguchi
Jun
J
Second Department of Surgery, Gunma University Faculty of Medicine, Gunma 371-8511, Japan. junhorig@showa.gunma-u.ac.jp
Yoshida
Takashi
T
Koibuchi
Yukio
Y
Iijima
Kotaro
K
Ninomiya
Jun
J
Takei
Hiroyuki
H
Yokoe
Takao
T
Iino
Yuichi
Y
Morishita
Yasuo
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014183:Transplantation, Heterologous
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil