Immunohistochemical determination of p53 protein does not predict clinical response in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil-leucovorin combination.
BACKGROUND
We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination.


METHODS
The study population consisted of 41 patients with unresectable metastatic colon cancer, homogeneously, treated with bolus 5-FU and LV.


RESULTS
Twenty-seven patients (66%) showed high levels of TS expression. The difference in the proportion of objective responses between patients with low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27) TS levels was statistically significant (P = 0.0001, chi-square test). p53 nuclear over-expression was found in 27 of 41 patients (66%). No differences were observed in p53 overexpression in patients with high (66%) or low (66%) TS expression. p53 status was not found to be associated with response even in patients with low TS expression.


CONCLUSIONS
p53 status measured by immunohistochemistry does not seem to be useful to identify unresponsive patients with low TS expression.
Cascinu
S
S
Department of Medical Oncology, Azienda Ospedaliera di Parma, Italy. cascinu@yahoo.com
Catalano
V
V
Aschele
C
C
Barni
S
S
Debernardis
D
D
Gallo
L
L
Bandelloni
R
R
Staccioli
M P
MP
Baldelli
A M
AM
Brenna
A
A
Valenti
A
A
Muretto
P
P
Catalano
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013940:Thymidylate Synthase / Q000032:analysis* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil