Abstract
We have investigated dihydropyrimidine dehydrogenase expression as a prognostic marker in breast cancer. A total of 119 women with breast cancer undergoing surgery between 1985 and 1996 were included in this study. Eighty-seven patients were treated with postoperative chemotherapy including 5-fluorouracil or 5-fluorouracil derivatives. Fifty-nine (50%) of 119 patients were determined to be immunostaining-positive for dihydropyrimidine dehydrogenase. There was no significant difference between dihydropyrimidine dehydrogenase staining and tumour size, lymph node status, clinical stage, oestrogen receptor status, histologic grade, or 5-fluorouracil administration. When evaluated in patients treated with 5-fluorouracil or 5-fluorouracil derivatives, patients with dihydropyrimidine dehydrogenase-positive tumours had a significantly (P<0.05) poorer disease-free survival compared to those with dihydropyrimidine dehydrogenase-negative tumour. No conclusion can be drawn about the prognostic impact of dihydropyrimidine dehydrogenase status in patients who were not treated with 5-fluorouracil regimes due to the small number of such cases in this series. Lymph node and dihydropyrimidine dehydrogenase status were independent prognostic factors for disease-free survival, and lymph node status for overall survival using multivariate analysis. In conclusion, dihydropyrimidine dehydrogenase is a possible prognostic factor in patients with breast cancer treated with 5-fluorouracil or 5-fluorouracil derivatives.British Journal of Cancer (2002) 86, 222–225. DOI: 10.1038/sj/bjc/6600040 www.bjcancer.com© 2002 The Cancer Research Campaign
Highlights
PATIENTS AND METHODSA total of 119 women with breast cancer undergoing surgery between 1985 and 1996 were studied
Immunohistochemistry has the advantage of permitting the evaluation of protein expression in situ using paraffin-embedded blocks of specimens
There was no significant difference between dihydropyrimidine dehydrogenase (DPD) staining and tumour size, lymph node status, clinical stage, ER status, histologic grade, or 5-FU and/or tamoxifen administration (Table 1)
Summary
A total of 119 women with breast cancer undergoing surgery between 1985 and 1996 were studied. The rhDPD polyclonal antibody (generously supplied by Dr Fukushima, Taiho Pharmaceutical Co., Ltd.) was used as a primary antibody This is an antibody highly specific against rhDPD expressed in the baculovirus-expression system using human DPD cDNA. The expressed rhDPD protein has been found to retain the entire molecular form and to show a high 5-FU-degrading activity equivalent to that of the human liver DPD. Using this recombinant protein, polyclonal antibody was generated and investigated for its specificity, relationship to enzyme activity and the possibility of immunohistochemical measurement of tumoral DPD.
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