PT - JOURNAL ARTICLE AU - Kawanishi, Aya AU - Hirabayashi, Kenichi AU - Yamada, Misuzu AU - Takanashi, Yumi AU - Hadano, Atsuko AU - Kawaguchi, Yoshiaki AU - Nakagohri, Toshio AU - Nakamura, Naoya AU - Mine, Tetsuya TI - Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma AID - 10.1136/jclinpath-2016-204028 DP - 2017 Jul 01 TA - Journal of Clinical Pathology PG - 619--624 VI - 70 IP - 7 4099 - http://jcp.bmj.com/content/70/7/619.short 4100 - http://jcp.bmj.com/content/70/7/619.full SO - J Clin Pathol2017 Jul 01; 70 AB - Aims 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.