Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival.
OBJECTIVE
We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy.


METHODS
Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1.


RESULTS
Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003).


CONCLUSIONS
The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.
Lenz
H J
HJ
Department of Medicine, University of Southern California School of Medicine, Los Angeles, USA.
Leichman
C G
CG
Danenberg
K D
KD
Danenberg
P V
PV
Groshen
S
S
Cohen
H
H
Laine
L
L
Crookes
P
P
Silberman
H
H
Baranda
J
J
Garcia
Y
Y
Li
J
J
Leichman
L
L
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D002945:Cisplatin / Q000008:administration & dosage; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005773:Gastroscopy; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil