Impact of orotate phosphoribosyl transferase activity as a predictor of lymph node metastasis in gastric cancer.
Orotate phosphoribosyl transferase (OPRT) is an essential nucleotide metabolic enzyme for cell proliferation and also a key enzyme for conversion of 5-FU to its active form in tumor tissue. The association between tumor OPRT activity and pathophysiological status, including lymph node metastasis [pN+], and the impact of OPRT for predicting pN+ were investigated in gastric cancer. The lymph node status of 73 resectable gastric cancer patients was analyzed preoperatively by computed tomography (CT), ultrasonography and magnetic resonance, and the OPRT activity of collected tumor tissue was measured. Then these data were compared with pathological observation of a surgical lymph node specimen. OPRT activity in the tumor tissue decreased as the depth of invasion increased. An OPRT test demonstrated superior sensitivity and comparable accuracy and sensitivity for predicting pN+, against current imaging diagnoses. Furthermore, the analysis of node negative patients by CT revealed that 80% of false negative patients were retrieved by this OPRT test. Thus, OPRT activity in tumor tissue was a powerful predictor of pN+ in resectable gastric cancer, and the preoperative OPRT test, when it becomes possible, would provide a basis for accurate evaluation of disease status, which is indispensable for the planning of personalized therapy.
Ochiai
Takumi
T
Department of Surgery, Toubu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, 5-14-1 Kameari, Katsushika-ku, Tokyo 125-8512, Japan. takumi-o@ma.kitanet.ne.jp
Sugitani
Michiharu
M
Nishimura
Kazuhiko
K
Noguchi
Hajime
H
Okada
Tsuyoshi
T
Ouchi
Masakazu
M
Yamada
Masaki
M
Kitajima
Masayuki
M
Tsuruoka
Yuko
Y
Takahashi
Yuka
Y
Futagawa
Shunji
S
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D014463:Ultrasonography
D000970:Antineoplastic Agents; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil