title: Impact of immunohistochemically identified lymphatic invasion on nodal metastasis in early gastric cancer.
abstract: BACKGROUND
  Among various clinical and pathological findings, lymphatic invasion (Ly) is the strongest risk factor for nodal metastasis in gastric cancer. However, the diagnosis of Ly is subjective and often inaccurate because of the difficulty of detecting lymphatic vessels with conventional hematoxylin and eosin (HE) staining.
  
  
  METHODS
  The distribution of lymphatics in the normal gastric wall was immunohistochemically characterized using a new selective marker of lymphatic endothelium, D2-40, in surgical specimens resected for early gastric cancer (EGC). Then, Ly in the primary lesion was reevaluated, and the positive (PPV) and negative (NPV) predictive values for nodal metastasis were comparatively examined for Ly detected by HE staining (Ly-HE) and by immunohistochemical staining (Ly-IM) in 131 cases of EGC.
  
  
  RESULTS
  D2-40-positive lymphatic vessels were observed in the deep proper mucosal layer, and the lymphatic vessel density (LVD) was extremely high in the muscularis mucosa (MM) layer. The number of Ly-IM-positive cases (15/131) was higher than the Ly-HE-positive cases (10/131). In 48 cases of intestinal-type cancer, Ly-IM had a PPV of 33.3% (2/6) and anNPV of 100% (42/42), which was more accurate than the corresponding figures for Ly-HE (25% and 98%, respectively). In contrast, the accuracy of Ly-IM was similar to that of Ly-HE in 83 cases of diffuse-type cancer.
  
  
  CONCLUSIONS
  Lymphatic vessels are most densely distributed in the MM layer in the gastric wall. Immunohistochemical identification of lymphatics is useful to increase the accuracy of diagnosing Ly in resected gastric EGCs. Ly-IM is superior to Ly-HE as a predictor of nodal metastasis, at least for intestinal-type EGC.
authors.affiliation: Department of Surgical Oncology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sako
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Yamashita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000556:secondary* / Q000601:surgery; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018279:Carcinoma, Signet Ring Cell / Q000276:immunology / Q000556:secondary* / Q000601:surgery; D004729:Endothelium, Lymphatic / Q000473:pathology; D005189:False Positive Reactions; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology* / Q000601:surgery
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C500987:monoclonal antibody D2-40