title: Intratumoral but not peritumoral lymphatic vessel density measured by D2-40 expression predicts poor outcome in gastric cancer--ROC curve analysis to find cut-off point.
abstract: BACKGROUND
  Neolymphangiogenesis, a process of lymphatic vessel development in neoplastic tissue, may be a key event in the transmission of cancer cells into lymph nodes. The current study examined the relationship between lymphatic vessel density (LVD) measured by podoplanin (D2-40) expression, clinicopathological parameters and patient survival in gastric cancer.
  
  
  METHODS
  D2-40 expression was examined by immunohistochemistry in formalin-fixed paraffin-embedded tissue specimens obtained from 60 patients with gastric cancer. D2-40 immunoreactivity was analyzed in intratumoral and peritumoral compartments of tumors and correlated with tumor grade, type in Lauren's classification, lymph node status, distant metastasis, presence of ulceration, inflammatory infiltration, angio-invasion, lymphangio-invasion and patient survival using a Receiver Operating Characteristic (ROC) curve analysis to find cut-off points that enabled fair decision making in survival analysis.
  
  
  RESULTS
  The mean values of intratumoral and peritumoral LVD were 6.63 and 11.25, respectively. Enhanced intratumoral LVD measured by D2-40 immunoexpression was correlated with the presence of lymph node metastases (p=0.04). Our study revealed a statistically significant correlation between intratumoral LVD measured by D2-40 expression and survival of patients with gastric cancer: an intratumoral LVD higher than 4.68 is significantly correlated with unfavorable prognosis, with a probability of death of approximately 80%. No significant relationship was identified between peritumoral LVD, lymph node status and survival in patients with gastric cancer.
  
  
  CONCLUSIONS
  A high intratumoral LVD measured by D2-40 expression in specimens from primary tumors is strongly associated with lymph node metastasis and predicts worse clinical outcome. Increased intratumoral D2-40 immunoreactivity is a putative predictor of aggressive gastric cancer behavior.
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland piotrdonizy@wp.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Donizy
authors.affiliation: Second Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Julia
authors.initials: J
authors.lastname: Rudno-Rudzinska
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Halon
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Dziegala
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jedrzej
authors.initials: J
authors.lastname: Kabarowski
authors.affiliation: Second Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Frejlich
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland Department of Physiotherapy, Wroclaw University School of Physical Education, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
authors.affiliation: Second Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kielan
authors.affiliation: Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, Wroclaw, Poland Lower Silesian Oncology Centre, Wroclaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Matkowski
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D000098853:Podoplanin
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin; C500987:monoclonal antibody D2-40
keywords: D2-40; gastric cancer; immunohistochemistry; podoplanin; prognostic marker