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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma

Authors: Ming-Chun Ma, Yi-Ju Chen, Tai-Jan Chiu, Jui Lan, Chien-Ting Liu, Yi-Ching Chen, Hsin-Ho Tien, Yen-Yang Chen

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Post-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC.

Methods

We retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections. MK expression was assessed in post-surgical immunohistochemical studies of specimens in paraffin blocks. Clinical outcomes were analyzed from medical records.

Results

Two-year disease-free and three-year overall survival rates were 42.1% and 44.6%. MK was expressed in 30 patients. Univariate analysis showed patients positively expressing MK had a significantly poorer 2-year disease free and three-year overall survival. Multivariate analysis found positive MK expression independently predicted recurrence.

Conclusions

Positive expression of MK predicts poor prognosis in patients with resectable CHCC-CC.
Literature
1.
Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L. Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer. 1985;55:124–35.CrossRefPubMed
2.
3.
Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, et al. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer. 2002;94:2040–6.CrossRefPubMed
4.
Liu CL, Fan ST, Lo CM, Ng IO, Lam CM, et al. Hepatic resection for combined hepatocellular and cholangiocarcinoma. Arch Surg. 2003;138:86–90.CrossRefPubMed
5.
Liver Cancer Study Group of J. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Ann Surg. 1990;211:277–87.
6.
Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M. Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol. 1995;26:956–64.CrossRefPubMed
7.
Ng IO, Shek TW, Nicholls J, Ma LT. Combined hepatocellular-cholangiocarcinoma: a clinicopathological study. J Gastroenterol Hepatol. 1998;13:34–40.CrossRefPubMed
8.
Taguchi J, Nakashima O, Tanaka M, Hisaka T, Takazawa T, et al. A clinicopathological study on combined hepatocellular and cholangiocarcinoma. J Gastroenterol Hepatol. 1996;11:758–64.CrossRefPubMed
9.
Yano Y, Yamamoto J, Kosuge T, Sakamoto Y, Yamasaki S, et al. Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases. Jpn J Clin Oncol. 2003;33:283–7.CrossRefPubMed
10.
Zhang F, Chen XP, Zhang W, Dong HH, Xiang S, et al. Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology. 2008;52:224–32.CrossRefPubMed
11.
Tickoo SK, Zee SY, Obiekwe S, Xiao H, Koea J, et al. Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. Am J Surg Pathol. 2002;26:989–97.CrossRefPubMed
12.
Yap AQ, Chen CL, Yong CC, Kuo FY, Wang SH, et al. Clinicopathological factors impact the survival outcome following the resection of combined hepatocellular carcinoma and cholangiocarcinoma. Surg Oncol. 2013;22:55–60.CrossRefPubMed
13.
Kim R, Kim SB, Cho EH, Park SH, Park SB, et al. CD44 expression in patients with combined hepatocellular cholangiocarcinoma. Ann Surg Treat Res. 2015;89:9–16.CrossRefPubMedPubMedCentral
14.
Kim GJ, Kim H, Park YN. Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma. PLoS One. 2013;8:e75449.CrossRefPubMedPubMedCentral
15.
16.
Ota K, Fujimori H, Ueda M, Jono H, Shinriki S, et al. Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma. Int J Oncol. 2010;37:797–804.PubMed
17.
18.
Salama RH, Muramatsu H, Zou P, Okayama M, Muramatsu T. Midkine, a heparin-binding growth factor, produced by the host enhances metastasis of Lewis lung carcinoma cells. Cancer Lett. 2006;233:16–20.CrossRefPubMed
19.
Rawnaq T, Dietrich L, Wolters-Eisfeld G, Uzunoglu FG, Vashist YK, et al. The multifunctional growth factor midkine promotes proliferation and migration in pancreatic cancer. Mol Cancer Res. 2014;12:670–80.CrossRefPubMed
20.
Luo J, Wang X, Xia Z, Yang L, Ding Z, et al. Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK). Mol Biol Cell. 2015;26:430–9.CrossRefPubMedPubMedCentral
21.
Sakamoto K, Kadomatsu K. Midkine in the pathology of cancer, neural disease, and inflammation. Pathol Int. 2012;62:445–55.CrossRefPubMed
22.
Chiu TJ, Chen YJ, Rau KM, Chen CH, Chien CY, et al. Midkine neurite growth-promoting factor 2 expression as a potential prognostic marker of adjuvant therapy in head and neck squamous cell carcinoma. Biomarkers. 2013;18:687–98.CrossRefPubMed
23.
Shimada H, Nabeya Y, Tagawa M, Okazumi S, Matsubara H, et al. Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma. Cancer Sci. 2003;94:628–32.CrossRefPubMed
24.
Yuan K, Chen Z, Li W, Gao CE, Li G, et al. MDK protein overexpression correlates with the malignant status and prognosis of non-small cell lung cancer. Arch Med Res. 2015;46:635–41.CrossRefPubMed
25.
Kato M, Shinozawa T, Kato S, Awaya A, Terada T. Increased midkine expression in hepatocellular carcinoma. Arch Pathol Lab Med. 2000;124:848–52.PubMed
26.
Kato M, Shinozawa T, Kato S, Endo K, Terada T. Increased midkine expression in intrahepatic cholangiocarcinoma: immunohistochemical and in situ hybridization analyses. Liver. 2000;20:216–21.CrossRefPubMed
27.
Greene FL, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging handbook : from the AJCC cancer staging manual. New York: Springer; 2002. p. xv. 469CrossRef
28.
Kim KH, Lee SG, Park EH, Hwang S, Ahn CS, et al. Surgical treatments and prognoses of patients with combined hepatocellular carcinoma and cholangiocarcinoma. Ann Surg Oncol. 2009;16:623–9.CrossRefPubMed
29.
Sanada Y, Shiozaki S, Aoki H, Takakura N, Yoshida K, et al. A clinical study of 11 cases of combined hepatocellular-cholangiocarcinoma assessment of enhancement patterns on dynamics computed tomography before resection. Hepatol Res. 2005;32:185–95.CrossRefPubMed
30.
Toh CH, Cheung YC, Ng SH, Lin CY, Chan SC, et al. Combined hepatocellular-cholangiocarcinoma: a case report. Int J Clin Pract. 2004;58:1170–3.CrossRefPubMed
31.
Lee SD, Park SJ, Han SS, Kim SH, Kim YK, et al. Clinicopathological features and prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgery. Hepatobiliary Pancreat Dis Int. 2014;13:594–601.CrossRefPubMed
32.
Lin G, Toh CH, Wu RC, Ko SF, Ng SH, et al. Combined hepatocellular cholangiocarcinoma: prognostic factors investigated by computed tomography/magnetic resonance imaging. Int J Clin Pract. 2008;62:1199–205.CrossRefPubMed
33.
Yoon YI, Hwang S, Lee YJ, Kim KH, Ahn CS, et al. Postresection outcomes of combined hepatocellular carcinoma-cholangiocarcinoma, hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2016;20:411–20.CrossRefPubMed
34.
Kadomatsu K, Kishida S, Tsubota S. The heparin-binding growth factor midkine: the biological activities and candidate receptors. J Biochem. 2013;153:511–21.CrossRefPubMed
35.
Shimada H, Nabeya Y, Okazumi S, Matsubara H, Kadomatsu K, et al. Increased serum midkine concentration as a possible tumor marker in patients with superficial esophageal cancer. Oncol Rep. 2003;10:411–4.PubMed
36.
Tanabe K, Matsumoto M, Ikematsu S, Nagase S, Hatakeyama A, et al. Midkine and its clinical significance in endometrial carcinoma. Cancer Sci. 2008;99:1125–30.CrossRefPubMed
37.
Obata Y, Kikuchi S, Lin Y, Yagyu K, Muramatsu T, et al. Serum midkine concentrations and gastric cancer. Cancer Sci. 2005;96:54–6.CrossRefPubMed
38.
Ibusuki M, Fujimori H, Yamamoto Y, Ota K, Ueda M, et al. Midkine in plasma as a novel breast cancer marker. Cancer Sci. 2009;100:1735–9.CrossRefPubMed
39.
Li F, Tian P, Zhang J, Kou C. The clinical and prognostic significance of midkine in breast cancer patients. Tumour Biol. 2015;36:9789–94.CrossRefPubMed
40.
Zhu WW, Guo JJ, Guo L, Jia HL, Zhu M, et al. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin Cancer Res. 2013;19:3944–54.CrossRefPubMed
41.
Komuta M, Spee B, Vander Borght S, De Vos R, Verslype C, et al. Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin. Hepatology. 2008;47:1544–56.CrossRefPubMed
42.
Villanueva A, Hoshida Y, Toffanin S, Lachenmayer A, Alsinet C, et al. New strategies in hepatocellular carcinoma: genomic prognostic markers. Clin Cancer Res. 2010;16:4688–94.CrossRefPubMedPubMedCentral
43.
Cai X, Zhai J, Kaplan DE, Zhang Y, Zhou L, et al. Background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma. Hepatology. 2012;56:1804–16.CrossRefPubMedPubMedCentral
44.
Li ZS, Li Q. The latest 2010 WHO classification of tumors of digestive system. Zhonghua Bing Li Xue Za Zhi. 2011;40:351–4.PubMed
45.
Gungor C, Zander H, Effenberger KE, Vashist YK, Kalinina T, et al. Notch signaling activated by replication stress-induced expression of midkine drives epithelial-mesenchymal transition and chemoresistance in pancreatic cancer. Cancer Res. 2011;71:5009–19.CrossRefPubMed
46.
Takenaka H, Horiba M, Ishiguro H, Sumida A, Hojo M, et al. Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction. Am J Physiol Heart Circ Physiol. 2009;296:H462–9.CrossRefPubMed
47.
Lee CW, Chan KM, Lee CF, Yu MC, Lee WC, et al. Hepatic resection for hepatocellular carcinoma with lymph node metastasis: clinicopathological analysis and survival outcome. Asian J Surg. 2011;34:53–62.CrossRefPubMed
Metadata
Title
Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma
Authors
Ming-Chun Ma
Yi-Ju Chen
Tai-Jan Chiu
Jui Lan
Chien-Ting Liu
Yi-Ching Chen
Hsin-Ho Tien
Yen-Yang Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4146-7

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