title: Molecular markers predicting lymph node metastasis in early esophageal cancer.
abstract: OBJECTIVE
  The aim of this study was to identify molecular markers predicting depth of tumor infiltration and presence of lymph node metastasis in early esophageal cancer.
  
  
  METHODS
  Between 1996 and 2004, 67 patients with pT1 esophagus cancer underwent esophagectomy. Resected tumors and lymph nodes were analyzed by immunohistochemistry for tissue infiltration, lymph node metastasis (LNM), micrometastasis and extracapsular lymph node infiltration (ELNI). We focused on MMP-2 (matrix-metalloproteinase-2), TIMP-2 (tissue inhibitor of metalloproteinase-2), PIM-1 and survivin as the most promising marker candidates. The data was correlated with the patients' long term follow-up (median follow-up time 11.4 years).
  
  
  RESULTS
  We found 22 pT1a and 45 pT1b carcinomas. None of the mucosal carcinomas, but 58% (26 patients) of the submucosal carcinomas showed lymph node metastasis or micrometastasis. The rate of LNM positively correlated with the depth of tumor infiltration (23% LNM in sm1 tumors and 82% LNM in sm3 tumors). Low grade PIM-1 expression (<30%) was significantly associated with occurrence of LNM (p=0.034) while high expression TIMP-2 (>70%) were detected in submucosal tumors. Logistic regression analysis revealed PIM-1 and Grading G3 as independent risk factors for LNM (p<0.001). Survival of patients with micrometastasis was comparable to those with LNM (median survival: 5.05 years versus 5.52 years). Patients with ELNI had the worst prognosis (median survival: 1.7 years).
  
  
  CONCLUSIONS
  PIM-1 is a promising marker for prediction of lymph node metastasis in early esophagus cancer. Extracapsular lymph node infiltration has an independent worse prognostic impact.
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Patrick S
authors: PS
authors: Plum
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Ute
authors: U
authors: Warnecke-Eberz
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Oulfa
authors: O
authors: Dhaouadi
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Hakan
authors: H
authors: Alakus
authors: Institute of Pathology, University of Cologne, Cologne, Germany.
authors: Uta
authors: U
authors: Drebber
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Ralf
authors: R
authors: Metzger
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Klaus L
authors: KL
authors: Prenzel
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany.
authors: Arnulf H
authors: AH
authors: Hölscher
authors: Department of General, Visceral and Cancer Surgery, University of Cologne, Germany. Elfriede.Bollschweiler@uk-koeln.de.
authors: Elfriede
authors: E
authors: Bollschweiler
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016629:Esophagectomy; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism; D015996:Survival Rate; D000077022:Survivin; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D051573:Proto-Oncogene Proteins c-pim-1; D020778:Matrix Metalloproteinase 2