Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.
We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.
Boku
N
N
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
Chin
K
K
Hosokawa
K
K
Ohtsu
A
A
Tajiri
H
H
Yoshida
S
S
Yamao
T
T
Kondo
H
H
Shirao
K
K
Shimada
Y
Y
Saito
D
D
Hasebe
T
T
Mukai
K
K
Seki
S
S
Saito
H
H
Johnston
P G
PG
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005982:Glutathione Transferase / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000032:analysis / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016228:Endothelial Growth Factors; D007527:Isoenzymes; D008222:Lymphokines; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013940:Thymidylate Synthase; D005982:Glutathione Transferase; D002945:Cisplatin; D005472:Fluorouracil