title: Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  The loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Immunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained.
  
  
  RESULTS
  Necl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p<0.001). Negative Necl-4 expression was significantly associated with a larger tumour size of >30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB-IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, p<0.001).
  
  
  CONCLUSIONS
  The results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kawanishi
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirabayashi
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Takanashi
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hadano
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakagohri
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; C498601:CADM4 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins
keywords: CELL ADHESION MOLECULES; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; PANCREATIC CANCER