Expression of dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase and thymidylate synthase in patients with primary colorectal cancer, and associations with site of first metastasis.
OBJECTIVE
The activity of the widely used anticancer drug 5-fluorouracil (5-FU) is determined by the presence of several enzymes, including dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), and thymidylate synthase (TS). This study compared the expression levels of these enzymes between primary colorectal cancer with and without distant metastases, and examined whether these expression patterns are associated with hematogenous metastasis.


METHODS
Among 40 patients with colorectal cancer, 20 had no metastasis and 20 had distant metastasis. Strong expression on immunohistochemistry was classified as positive, while weak, moderate or no expression was classified as negative.


RESULTS
Positive expressions of DPD, OPRT and TS in primary colorectal cancer tissue were seen in 47.5%, 75% and 20%, respectively. However, no relationships were observed among the expressions of DPD, OPRT and TS. Expressions of OPRT (p=0.029) and TS (p=0.017) in primary tissues were significantly associated with hematogenous metastasis. Patterns of the expression of the three enzymes varied, and were classified in six ways. A tendency was seen for primary colorectal cancer with DPD-high expression to have liver metastasis and for that with DPD-low expression, to have lung metastasis.


CONCLUSIONS
High expression levels of OPRT and TS in colorectal cancer appear to be significantly involved in metastasis after curative surgery. The organs in which metastases arise may be controlled by the expression of DPD.
Department of Surgery, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan. yoshisg@med.kurume-u.ac.jp
Yoshito
Y
Akagi
Tetsushi
T
Kinugasa
Tomoaki
T
Mizobe
Akihiko
A
Kawahara
Masayoshi
M
Kage
Kazuo
K
Shirouzu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D055815:Young Adult
D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase