Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma
Clinicopathological significance of Necl-4 expression in pancreatic ductal adenocarcinoma
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DOI：
10.1136/jclinpath-2016-204028
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发表时间：
2017-07-01
影响因子：
3.4
通讯作者：
Mine, Tetsuya
中科院分区：
文献类型：
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作者：
Kawanishi, Aya;Hirabayashi, Kenichi;Mine, Tetsuya
Nectin样分子4（Necl-4;一种免疫球蛋白样细胞粘附分子）的缺失或表达降低与某些类型癌症的发生和进展有关。方法采用免疫组化方法检测258例胰腺导管腺癌（PDAC）组织芯片中Necl-4和E-cadherin的表达，并分析其与PDAC的临床病理学关系。还评估了组织微阵列核心中包括的38个胰腺上皮内瘤变（PanIN）病变的Necl-4表达。结果118例PDAC中Necl-4阳性表达率为45.7%（n=118），阴性表达率为54.3%（n=140）。Necl-4染色在低级别PanIN病例中为96.7%（n=29）的阳性和3.3%（n=1）的阴性，在高级别PanIN病例中为62.5%（n=5）的阳性和37.5%（n=3）的阴性。Necl-4阳性表达的病例数按低级别PanIN>高级别PanIN> PDAC的顺序减少（p< 0.001）。Necl-4阴性表达与> 30 mm的较大肿瘤尺寸、神经周围浸润、淋巴受累、淋巴结转移（pN 1）、晚期TNM（肿瘤、淋巴结、转移）分期（IIB-IV期）、晚期组织学分级（G2/3）和较短的总生存期显著相关。PDAC中E-cadherin染色阳性率为46.1%（n=118），阴性率为53.9%（n=138）。Necl-4与E-cadherin表达呈正相关（r=0.405，p< 0.001）。
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.