The diagnostic and prognostic value of MRP8/MRP14 in intrahepatic cholangiocarcinoma.

Guang-Zhi Jin,Wen-Long Yu,Ai-Jun Li,Wen-Ming Cong,Wei Dong,Meng-Chao Wu,Hua Yu,Hui Dong,Jia Chen

doi:10.18632/oncotarget.5329

Guang-Zhi Jin, Wen-Long Yu + Show 7 more

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https://doi.org/10.18632/oncotarget.5329

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Journal: Oncotarget	Publication Date: Oct 12, 2015
Citations: 40	License type: cc-by

Affiliation: Eastern Hepatobiliary Surgery Hospital

Abstract

Myeloid-related protein 8 (MRP8) and 14 (MRP14) are abundantly expressed in several kinds of benign and malignant tumors. However, little is known about their clinicopathological significance in intrahepatic cholangiocarcinoma (ICC), biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of bile duct (IPNB), or inflammatory hepatic biliary ducts epithelium (IHBD). This study aimed to investigate the diagnostic and prognostic values of MRP8 and MRP14 as new biomarkers for ICC. We examined MRP8 and MRP14 expression levels by immunohistochemistry in IHBD (n = 15), BilIN (BilIN1 = 24, BilIN2 = 9, BilIN3 = 5), IPNB (n = 18) and ICC (n = 416). The differential diagnostic and prognosis values were also evaluated. The results showed that the ratio of tumor-infiltrating MRP8 and MRP14 positive immune cells, relative to biliary epithelial cells, was significantly increased in ICC tissues compared with nonmalignant tissues, including IHBD, BilIN1, BilIN2, BilIN3, and IPNB (P value < 0.05). In addition, over-expression levels of MRP8 and MRP14 were correlated with overall survival (OS) and time to recurrence (TTR) by univariate analysis; MRP8/MRP14 combination was an independent prognostic factor for OS and TTR. MRP8 and MRP14 expression might help to identify the benign bile duct diseases from ICC, as high expression of MRP8 and MRP14 suggests a poor prognosis after surgical resection.

Highlights

Intrahepatic cholangiocarcinoma (ICC) is a poorly understood biliary malignancy that accounts for an estimated 10–15% of all primary liver cancers [1] and approximately 8% of cholangiocarcinomas [2]
The results showed that the ratio of tumor-infiltrating Myeloid-related protein 8 (MRP8) and MRP14 positive immune cells, relative to biliary epithelial cells, was significantly increased in intrahepatic cholangiocarcinoma (ICC) tissues compared with nonmalignant tissues, including inflammatory hepatic biliary ducts epithelium (IHBD), BilIN1, BilIN2, BilIN3, and intraductal papillary neoplasm of bile duct (IPNB) (P value < 0.05)
The expression level represented by the ratio of infiltrating MRP8 and MRP14 positive cells compared with the number of biliary epithelial cells was calculated

Summary

Introduction

Intrahepatic cholangiocarcinoma (ICC) is a poorly understood biliary malignancy that accounts for an estimated 10–15% of all primary liver cancers [1] and approximately 8% of cholangiocarcinomas [2]. In the United States, the age-adjusted incidence of ICC increased from 0.32 per 100,000 individuals in 1975 to 0.85 per 100,000 individuals in 2000, and is still increasing [3, 4]. Biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of bile duct (IPNB) are two proposed benign bile duct diseases for the development and progression of ICC. Partial hepatectomy remains the gold standard of curative treatment for ICC [7, 8]. Prognosis after partial hepatectomy is unsatisfactory, with a high incidence of locoregional recurrence and/or distant metastases [9,10,11]. Identifying effective novel prognostic biomarkers that might be related to the development and progression of ICC may help provide new therapeutic strategies

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