PMID- 9440758
OWN - NLM
STAT- MEDLINE
DCOM- 19980127
LR  - 20170210
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 16
IP  - 1
DP  - 1998 Jan
TI  - ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting 
      response and survival for gastric cancer patients receiving combination cisplatin 
      and fluorouracil chemotherapy.
PG  - 309-16
AB  - PURPOSE: We have previously shown that relative thymidylate synthase (TS) mRNA 
      levels in primary gastric adenocarcinomas treated with fluorouracil (5-FU) and 
      cisplatin are inversely associated with response and survival. This is a presumed 
      function of TS as a target for 5-FU activity. We now test the hypotheses that the 
      relative mRNA level of the excision repair cross-complementing (ERCC1) gene is 
      inversely associated with response and survival as an independent function of 
      cisplatin efficacy. PATIENTS AND METHODS: Patients had intact, untreated, primary 
      gastric adenocarcinoma cancer and were evaluated for eligibility on a 
      preoperative cisplatin infusion-5-FU protocol. cDNA, derived from primary gastric 
      tumors before chemotherapy, was used to determine ERCC1 mRNA levels, expressed as 
      the ratio of polymerase chain reaction (PCR) product of the ERCC1 gene and the 
      beta-actin gene. RESULTS: The median ERCC1 mRNA level from 38 primary gastric 
      cancers (33 assessable for response) was 5.8 x 10(-3) (range, 1.8 x 10(-3) to 
      19.5 x 10(-3)). Of 17 responding patients, 13 (76%) were less than or equal to 
      5.8 x 10(-3) and four were greater than 5.8 x 10(-3) (P = .003). The median 
      survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3) 
      has not been reached, whereas for those greater than 5.8 x 10(-3) it was 5.4 
      months (P = .034). The median TS mRNA level, 3.7 x 10(-3) (range, 0.9 to 18.9) 
      also segregated responsive versus resistant tumors (P = .024). With both ERCC1 
      and TS mRNA levels below their medians, 11 of 13 patients (85%) responded; with 
      both ERCC1 and TS mRNA levels above their medians, two of 10 patients (20%) 
      responded (P = .003). CONCLUSION: Considered separately, either ERCC1 or TS mRNA 
      levels in a primary gastric adenocarcinoma has a statistically significant 
      relationship to response. ERCC1 mRNA levels have a statistically significant 
      association with survival; in this cohort TS mRNA levels did not reach 
      statistically significant association with survival as in our previous 
      publication. Whether these molecular parameters are independent of each other as 
      predictors of outcome remains to be determined.
FAU - Metzger, R
AU  - Metzger R
AD  - University of Southern California/Norris Comprehensive Cancer Center, Los 
      Angeles, CA 90033, USA.
FAU - Leichman, C G
AU  - Leichman CG
FAU - Danenberg, K D
AU  - Danenberg KD
FAU - Danenberg, P V
AU  - Danenberg PV
FAU - Lenz, H J
AU  - Lenz HJ
FAU - Hayashi, K
AU  - Hayashi K
FAU - Groshen, S
AU  - Groshen S
FAU - Salonga, D
AU  - Salonga D
FAU - Cohen, H
AU  - Cohen H
FAU - Laine, L
AU  - Laine L
FAU - Crookes, P
AU  - Crookes P
FAU - Silberman, H
AU  - Silberman H
FAU - Baranda, J
AU  - Baranda J
FAU - Konda, B
AU  - Konda B
FAU - Leichman, L
AU  - Leichman L
LA  - eng
GR  - R0-96111/PHS HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.1.1.45 (Thymidylate Synthase)
RN  - EC 3.1.- (ERCC1 protein, human)
RN  - EC 3.1.- (Endonucleases)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adenocarcinoma/chemistry/*drug therapy/*mortality/surgery
MH  - Cisplatin/administration & dosage
MH  - Combined Modality Therapy
MH  - *DNA-Binding Proteins
MH  - *Endonucleases
MH  - Female
MH  - Fluorouracil/administration & dosage
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction/methods
MH  - Prospective Studies
MH  - Proteins/*analysis/genetics
MH  - RNA, Messenger/analysis
MH  - Stomach Neoplasms/chemistry/*drug therapy/*mortality/surgery
MH  - Thymidylate Synthase/*analysis/genetics
EDAT- 1998/01/24 00:00
MHDA- 1998/01/24 00:01
CRDT- 1998/01/24 00:00
PHST- 1998/01/24 00:00 [pubmed]
PHST- 1998/01/24 00:01 [medline]
PHST- 1998/01/24 00:00 [entrez]
AID - 10.1200/JCO.1998.16.1.309 [doi]
PST - ppublish
SO  - J Clin Oncol. 1998 Jan;16(1):309-16. doi: 10.1200/JCO.1998.16.1.309.