p53, bcl-2 and thymidine phosphorylase as predictive markers of chemotherapy in patients with advanced and recurrent gastric cancer.
OBJECTIVE
To study the relationship between expression of p53, bcl-2, thymidine phosphorylase and Ki-67 and the response to chemotherapy and survival in patients with recurrent and advanced gastric cancer.


METHODS
Protein expression was assessed immunohistochemically in 28 patients treated with 5-fluorouracil, pirarubicin and cisplatin (FAP).


RESULTS
The response rate in patients positive for p53 expression was 23% compared with 47% of p53-negative patients. The response rate was also reduced from 44% in patients negative for bcl-2 protein expression to 25% in bcl-2 positive patients. Thymidine phosphorylase (dThdPase) expression was observed in 20 patients (71%), 50% of whom responded to chemotherapy, while patients negative for dThdPase expression did not respond to chemotherapy. The correlation between response rate and dThdPase-positivity was statistically significant (p < 0.05). However, with regard to patient survival, p53- and bcl-2-negative patients showed significantly better survival than patients positive for p53 and/or bcl-2 (p = 0.036).


CONCLUSIONS
While dThdPase expression may be a useful predictor of response to chemotherapies that include 5-FU, p53 and bcl-2 expression may predict the outcome of patients with recurrent and advanced gastric cancer following chemotherapy.
Kikuyama
S
S
Department of Surgery, Tochigi National Hospital, Japan. kikuyama@hh.iij4u.or.jp
Inada
T
T
Shimizu
K
K
Miyakita
M
M
Ogata
Y
Y
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015996:Survival Rate; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D013939:Thymidine Phosphorylase; D002945:Cisplatin; D005472:Fluorouracil