title: Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer.
abstract: BACKGROUND
  Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data.
  
  
  RESULTS
  All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004).
  
  
  CONCLUSIONS
  Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value.
authors.affiliation: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway. nood@sus.no
authors.forename: Oddmund
authors.initials: O
authors.lastname: Nordgård
authors.forename: Gurpartap
authors.initials: G
authors.lastname: Singh
authors.forename: Steinar
authors.initials: S
authors.lastname: Solberg
authors.forename: Lars
authors.initials: L
authors.lastname: Jørgensen
authors.forename: Ann Rita
authors.initials: AR
authors.lastname: Halvorsen
authors.forename: Rune
authors.initials: R
authors.lastname: Smaaland
authors.forename: Odd Terje
authors.initials: OT
authors.lastname: Brustugun
authors.forename: Åslaug
authors.initials: Å
authors.lastname: Helland
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D020224:Expressed Sequence Tags; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008198:Lymph Nodes / Q000378:metabolism* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D025341:Principal Component Analysis; D011379:Prognosis; D011446:Prospective Studies; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C527875:CEACAM5 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D058851:GPI-Linked Proteins; D053539:Keratin-19; D037662:Pulmonary Surfactant-Associated Protein A; D037721:Pulmonary Surfactant-Associated Protein C; C445842:SFTPA1 protein, human; C489679:SFTPC protein, human