PMID- 26220094
OWN - NLM
STAT- MEDLINE
DCOM- 20161111
LR  - 20181113
IS  - 1699-3055 (Electronic)
IS  - 1699-048X (Linking)
VI  - 18
IP  - 1
DP  - 2016 Jan
TI  - Thymidylate synthase gene amplification predicts pemetrexed resistance in 
      patients with advanced non-small cell lung cancer.
PG  - 107-12
LID - 10.1007/s12094-015-1359-y [doi]
AB  - BACKGROUND: Thymidylate synthase (TYMS) expression in lung cancer tissue affects 
      the therapeutic efficacy of pemetrexed (PMT). TYMS protein expression is 
      primarily assessed using immunohistochemistry (IHC), but this method is not 
      suitable for accurate quantitative analysis. It is not known whether the analysis 
      of TYMS gene copy number using fluorescence in situ hybridization (FISH) is a 
      useful method for assessment of TYMS expression. PATIENTS AND METHODS: The 
      participants were patients with chemo-naive advanced NSCLC treated with PMT plus 
      carboplatin (CBDCA) in prospective clinical phase II study. TYMS expression was 
      evaluated in 40 patients by gene copy number and protein expression using FISH 
      and IHC. Therapeutic efficacy was evaluated by investigating the response rate 
      (RR), disease control rate (DCR), progression-free survival (PFS), and overall 
      survival (OS). RESULTS: TYMS gene amplification was detected in 8 patients (32 %) 
      among 25 patients who could be evaluated for TYMS gene copy number. There were no 
      patients with complete or partial response in the TYMS amplified group. RR and 
      DCR were lower in the TYMS amplified group compared with the TYMS unamplified 
      group (0 versus 35.3 %, p = 0.0539, 62.5 versus 94.1 %, p = 0.0443). PFS and OS 
      were reduced in the TYMS amplified group. The analysis of TYMS gene copy number 
      had higher sensitivity and specificity compared with TYMS protein expression 
      (76.2 versus 50.0 %, 75.0 versus 66.7 %). CONCLUSION: The analysis of TYMS gene 
      copy number is more suitable than TYMS protein expression for assessment of TYMS 
      expression. TYMS gene amplification predicts outcome of patients receiving PMT 
      with advanced NSCLC.
FAU - Shimizu, T
AU  - Shimizu T
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Nihon 
      University School of Medicine, 30-1, Oyaguchi-Kamichou, Itabashi-ku, Tokyo, 
      173-8610, Japan. shimizu.tetsuo@nihon-u.ac.jp.
FAU - Nakagawa, Y
AU  - Nakagawa Y
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Nihon 
      University School of Medicine, 30-1, Oyaguchi-Kamichou, Itabashi-ku, Tokyo, 
      173-8610, Japan.
FAU - Takahashi, N
AU  - Takahashi N
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Nihon 
      University School of Medicine, 30-1, Oyaguchi-Kamichou, Itabashi-ku, Tokyo, 
      173-8610, Japan.
FAU - Hashimoto, S
AU  - Hashimoto S
AD  - Division of Respiratory Medicine, Department of Internal Medicine, Nihon 
      University School of Medicine, 30-1, Oyaguchi-Kamichou, Itabashi-ku, Tokyo, 
      173-8610, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20150729
PL  - Italy
TA  - Clin Transl Oncol
JT  - Clinical & translational oncology : official publication of the Federation of 
      Spanish Oncology Societies and of the National Cancer Institute of Mexico
JID - 101247119
RN  - 0 (Biomarkers, Tumor)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - EC 2.1.1.45 (TYMS protein, human)
RN  - EC 2.1.1.45 (Thymidylate Synthase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Biomarkers, Tumor/genetics
MH  - Carcinoma, Non-Small-Cell Lung/diagnosis/*drug therapy/genetics/pathology
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Female
MH  - *Gene Amplification
MH  - Gene Dosage
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/diagnosis/*drug therapy/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Pemetrexed/*administration & dosage
MH  - Prognosis
MH  - Thymidylate Synthase/*genetics
MH  - Young Adult
OTO - NOTNLM
OT  - Fluorescence in situ hybridization
OT  - Gene amplification
OT  - Immunohistochemistry
OT  - Pemetrexed
OT  - Thymidylate synthase
EDAT- 2015/07/30 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/07/30 06:00
PHST- 2015/06/04 00:00 [received]
PHST- 2015/07/11 00:00 [accepted]
PHST- 2015/07/30 06:00 [entrez]
PHST- 2015/07/30 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - 10.1007/s12094-015-1359-y [pii]
AID - 10.1007/s12094-015-1359-y [doi]
PST - ppublish
SO  - Clin Transl Oncol. 2016 Jan;18(1):107-12. doi: 10.1007/s12094-015-1359-y. Epub 
      2015 Jul 29.