title: Comparison of site-specific gene expression levels in primary tumors and synchronous lymph node metastases in advanced gastric cancer.
abstract: BACKGROUND
  Many malignant tumors consist of heterogeneous subpopulations of cells. This heterogeneity is associated with genetic characteristics. However, it remains unclear whether gene expression levels differ among specific sites of tumors in gastric cancer.
  
  
  METHODS
  We studied differences in gene expression levels among specific sites of primary tumors and synchronous lymph node metastases, using formalin-fixed, paraffin-embedded specimens resected surgically from 48 patients with previously untreated advanced gastric cancer. Specimens were obtained by laser-captured microdissection from five regions: (1) nonneoplastic mucosa, (2) surface layer (mucosa) of the primary tumor (surface sections), (3) middle layer (submucosa) of the primary tumor (middle sections), (4) the deepest layer of the primary tumor (muscularis propria or deeper) at the site of deepest invasion (deep sections), and (5) level 1 synchronous lymph node metastasis (lymph node metastases). Expression levels of the following target genes were determined by quantitative real-time polymerase chain reaction: thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF1α).
  
  
  RESULTS
  TP, DPD, EGFR, and HIF1α gene expression levels were significantly higher in deep sections than in surface sections. TP, EGFR, VEGF, and HIF1α gene expression levels were significantly higher in lymph node metastases than in surface sections. TP, DPD, EGFR, VEGF, and HIF1α gene expression levels were positively correlated with the specific samples harvested from the tumors.
  
  
  CONCLUSIONS
  Our results show that the expression levels of some genes in tumor cells can change in specific sites of tumors and can become higher in association with tumor progression.
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan, akira-n@kitasato-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Naruke
authors.forename: Mizutomo
authors.initials: M
authors.lastname: Azuma
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishido
authors.forename: Chikatoshi
authors.initials: C
authors.lastname: Katada
authors.forename: Tohru
authors.initials: T
authors.lastname: Sasaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Higuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Saegusa
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger