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. 2019 Apr;8(4):1671-1678.
doi: 10.1002/cam4.2016. Epub 2019 Feb 21.

Expression of SNAIL in accompanying PanIN is a key prognostic indicator in pancreatic ductal adenocarcinomas

Sho Fujiwara  1 , Yuriko Saiki  1 , Kota Ishizawa  1 , Shinichi Fukushige  1 , Mie Yamanaka  1 , Masaki Sato  1   2 , Masaharu Ishida  2 , Fuyuhiko Motoi  2 , Michiaki Unno  2 , Akira Horii  1
Affiliations

Expression of SNAIL in accompanying PanIN is a key prognostic indicator in pancreatic ductal adenocarcinomas

Sho Fujiwara et al. Cancer Med. 2019 Apr.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, mainly because of its invasive and metastatic characteristics. Pancreatic intraepithelial neoplasia (PanIN) is one of the major precursor lesions of PDAC. Although epithelial-to-mesenchymal transition (EMT) is known to play an important role for these malignant behaviors, the association between PanIN and EMT has not been clearly understood. Therefore, we explored possible molecules for regulation of EMT immunohistochemically. Using surgically resected specimens from 71 PDAC patients, expressions of SNAIL, SLUG, TWIST1, and ZEB1 were investigated in high-grade PanIN (HG-PanIN) and PDAC. Results demonstrated that PDAC accompanied by SNAIL-positive HG-PanIN showed a significantly better relapse-free survival (RFS) (median survival time (MST) of 11.3 months vs 4.4 months, P < 0.001) and overall survival overall survival (OS) (MST of 25.2 months vs 13.6 months, P < 0.001). In PDAC accompanied by SLUG-positive HG-PanIN, RFS and OS (P = 0.09 and P = 0.05) tended to have a better prognosis. In contrast, we could not find any significant prognostic benefits in the expression of TWIST1 or ZEB1 in PDAC accompanied by HG-PanIN. Our present results suggest that (1) EMT may play an important role in the development of PDAC from HG-PanIN, and (2) SNAIL may predict a distinct subgroup that shows a better prognosis.

Keywords: epithelial-to-mesenchymal transition; high-grade PanIN; pancreatic ductal adenocarcinoma; pancreatic intraepithelial neoplasia; prognosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Immunohistochemical staining results of EMT regulators in HG‐PanIN: SNAIL, SLUG, TWIST1, and ZEB1. We categorized and defined three grades: grade 0, <10% positive staining; grade 1, 10%‐50% positive; grade 2, 50%< positive
Figure 2
Figure 2
Expression of SNAIL and SLUG in HG‐PanIN and PDAC. Expression levels in PDAC regions were higher than those in HG‐PanIN, and expressions in invading PDAC regions are prominent
Figure 3
Figure 3
Expression levels of EMT regulators and relationships between HG‐PanIN and PDAC. All regulators’ expressions increased in PDAC compared with HG‐PanIN. There were statistically significant differences in SNAIL and SLUG, respectively
Figure 4
Figure 4
Kaplan‐Meier survival curves by expression status of each EMT regulator in accompanying HG‐PDAC and patients’ prognoses. (A‐D) RFS; and (E‐H) OS. SNAIL (A and E), SLUG (B and F), TWIST1 (C and G), ZEB1 (D and H)
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