title: Histopathologic determinants of regional lymph node metastasis in early colorectal cancer.
abstract: BACKGROUND
  Early colorectal cancer (ECC) is curable by endoscopic local resection; however, 10% of patients with ECC exhibit lymph node (LN) metastasis. In the current study, accurate predictors for LN metastasis in patients with ECC were examined by using immunohistochemistry with the lymphatic endothelial hyaluronan receptor 1 (LYVE-1) antibody to discriminate between lymphatics and blood vessels.
  
  
  METHODS
  Colorectal tissue specimens obtained from 71 patients with ECC, including 28 patients with regional LN metastasis, were immunostained with antibodies against LYVE-1, beta-catenin, claudin-3, claudin-4, and cytokeratin. The significance of the histopathologic variables for LN metastasis in ECC was investigated on the basis of specific histopathologic parameters.
  
  
  RESULTS
  Lymphatic invasion confirmed by LYVE-1 immunohistochemistry was observed mainly in the submucosal area around the primary tumor and rarely was observed in the tumor. Expression patterns of beta-catenin, claudin-3, and claudin-4 in cancer cells at the invasive front were irrelevant to LN status. Tumor size, depth of invasion, histologic tumor type, budding formation, and lymphatic invasion were statistically significant to LN status in univariate analysis; however, only 2 factors--lymphatic invasion and budding formation at the invasive front-were independent predictors of LN metastasis in ECC.
  
  
  CONCLUSIONS
  LYVE-1 immunohistochemistry appeared to be a useful method for detecting lymphatics invaded by cancer cells, and detailed examination of the submucosa around the tumor may be important for predicting LN metastasis. When lymphatic invasion and budding formation are observed histopathologically in patients with ECC, additional therapy, such as adjuvant chemotherapy or a curative resection of the regional LN, may be required.
authors.affiliation: Department of Pathology, Toho University School of Medicine, Tokyo, Japan. yukio@med.toho-u.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Yuri
authors.initials: Y
authors.lastname: Akishima-Fukasawa
authors.forename: Kinji
authors.initials: K
authors.lastname: Ito
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Akasaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yokoo
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D062465:Claudin-3; D062506:Claudin-4; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D011237:Predictive Value of Tests; D033921:Vesicular Transport Proteins / Q000032:analysis; D051176:beta Catenin / Q000032:analysis
chemical_list: C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062465:Claudin-3; D062506:Claudin-4; C119248:LYVE1 protein, human; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D051176:beta Catenin; D007633:Keratins