Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

ATSUSHI NANASHIMA,^1,2 GO HATACHI,¹ TETSUROU TOMINAGA,¹ GOUSHI MURAKAMI,¹ KATSUNORI TAKAGI,¹ JUNICHI ARAI,¹ HIDEO WADA,¹ TAKESHI NAGAYASU¹ and YORIHISA SUMIDA¹

¹Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan
²Division of Hepato-Biliary-Pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Miyazaki, Japan

Nogo-B, located in the endoplasmic reticulum, is an isoform belonging to the reticulon protein family, which is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis, but its distinct function in liver malignancies has not been fully clarified. We have hypothesized that Nogo-B expression may be altered in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. The present study aimed to investigate the relationship between Nogo-B expression, assessed by immunohistochemical staining, and clinicopathological factors and prognosis in 34 ICC patients. Positive expression was observed in 19 (56%) of 34 ICC specimens: 6 patients (18%) with positivity levels of 1+ (positive cells in 10-50% of cancer cells) and 13 patients (38%) with 2+ (positive cells over 50%). Importantly, the remaining 15 patients (44%) were categorized as negative expression (Nogo-B-positive cells, less than 10%). Conversely, the mass-forming type of ICC tended to express Nogo-B with the degree of 2+ positivity, compared to the periductal infiltration type (p = 0.064), and the mass-forming type showed a better 5-year survival rate (66% vs. 5%) after hepatectomy (p < 0.05). However, the degree of positivity was not associated with tumor relapse rate, disease-free and overall survival, although each of the periductal infiltration type, intrahepatic metastasis, larger tumor size, and lower microvessel counts was associated with lower survival rates. We propose that Nogo-B expression is down-regulated in ICC, the implication of which, however, remains to be investigated.

keywords —— cholangiole proliferation; hepatic resection; intrahepatic cholangiocarcinoma; macroscopic finding; Nogo-B

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Tohoku J. Exp. Med., 2016, 238, 9-16

Correspondence: Atsushi Nanashima M.D., Division of Hepato-Biliary-Pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, 5200 Kihara, Miyazaki, Miyazaki 889-1601, Japan.

e-mail: a_nanashima@med.miyazaki-u.ac.jp