Mm. Davies et al., Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine, CLIN CANC R, 5(2), 1999, pp. 325-328
We assessed whether intensity of colorectal liver metastasis staining with
the thymidylate synthase (TS) antibody TS106 predicted response to hepatic
arterial infusion (HAI) of floxuridine chemotherapy,
Liver metastasis biopsies were taken during laparotomy for hepatic arterial
cannulation and stained using the TS106 monoclonal antibody. Staining inte
nsity was designated at histological examination by two independent assesso
rs as either "high" or "low," Patients were treated by HAI, and li, er meta
stasis response was assessed by comparison of computed tomography scan tumo
r volume before and after 4 months of treatment,
A significant correlation (Fisher's exact test, P = 0.01) was noted between
partial response to HAI and TS106 staining intensity in patients with colo
rectal liver metastases. Seventy-five percent of patients with evidence of
a partial response had low TS staining compared with 29% of nonresponders.
There was a significant difference (Fisher's exact test, P = 0.01) in the p
roportion of low (9 of 16) compared with high (3 of 20) TS staining tumors
in which a partial response occurred. There was no significant difference (
logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatme
nt of high (median, 322 days; interquartile range, 236-411) compared with l
ow (median, 335 days; interquartile range, 301-547) TS staining patients.
This study demonstrates an inverse correlation between TS immunohistochemic
al staining intensity in colorectal liver metastases and response to HAI, T
he results suggest that a prospective assessment of TS staining intensity i
n colorectal liver metastases would be useful to determine whether this met
hod can be used to define patients who will benefit from HAI chemotherapy.