Characteristics of the expression level of MMP-9 and TIMP-1 in hepatocellular and cholangiocellular liver carcinoma

Authors

DOI:

https://doi.org/10.14739/2310-1237.2015.1.42819

Keywords:

Hepatocellular Carcinoma, Сholangiocellular Carcinoma, Mouse TIMP-1 Protein, Mouse MMP-9 Protein

Abstract

Aim. In order to determine the expression level of immunohistochemical markers of matrix metalloproteinase-9 (ММР-9) and its tissue inhibitor TIMP-1, and area of immunopositive cells а comprehensive histopathological, histological and immunohistochemical study of liver biopsy specimens was carried out in 94 patients, of which 55 (58.51%) patients had hepatocellular carcinoma and 39 (41.49%) – cholangiocellular carcinoma of liver.

Methods and results. In 92.73% of patients with hepatocellular carcinoma and in 89.74% of patients with cholangiocellular carcinoma in malignant cells cytoplasmic expression of MMP-9 was determined. MMP-9 immunopositive cells took 59,33±22,57% of area of the tissue section of hepatocellular carcinoma and 52,71±20,86% of area of the tissue section of cholangiocellular liver cancer. In 80% of hepatocellular carcinoma patients and 74.36% of patients with cholangiocellular carcinoma in tumor cells cytoplasmic expression of TIMP-1 was revealed. TIMP-1 immunopositive cells constituted 21,94±6,27% of area of the tissue section of hepatocellular liver cancer and 33,05±13,85% of area of the tissue section of holangiocellular liver cancer.

Conclusion. In both types of liver cancer direct strong relationship was noted between high levels of expression of MMP-9 by the tumor cells and low expression of TIMP-1, which indicates high invasive potential and aggressiveness of hepatocellular carcinoma and cholangiocellular carcinoma.

References

Malemud, C. J. (2006) Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci, 11, 1696–1701. doi: 10.2741/1915.

Visse, R., & Nagase, H. (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res, 92(8), 827–839. doi: 10.1161/01.RES.0000070112.80711.3D.

Joo, Y-E, Seo, Y-H, Lee, W-S, Kim, H-S, Choi, S-K, Rew, J-S, et al. (2000) Expression of Tissue Inhibitors of Metalloproteinases (TIMPs) in Hepatocellular Carcinoma. Korean J Intern Med., 15(3), 171–178.

French, J. J., Midwinter, M. J., Bennet, M. K., Manas, D. M., & Charley, R. M. (2005) A matrix metalloproteinase inhibitor to treat unresectable cholangiocarcinoma. HPB (Oxford), 7(4), 289–291. doi: 10.1080/13651820510042246.

Theret, N., Musso, O., Turlin, B., Lotrian, D., Bioulac-Sage, P., Campion, J.P., et al. (2001) Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Hepatology, 34(1), 82–88.

Ip, Y. C., Cheung, S. T., Leung, K. L., Fan, S. T. (2005) Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma. World J Gastroenterol, 11(40), 6269–6276. doi: 10.3748/wjg.v11.i40.6269.

Gao, Z. H., Tretiakova, M. S., Liu, W. H., Gong, C., Farris, P. D., & Hart, J. (2006) Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma. Mod Pathol., 19(4), 533–540.

Jan, YY., Yeh, TS., Yeh, JN., Yang, HR., & Chen, MF. (2004) Expression of Epidermal Growth Factor Receptor, Apomucins, Matrix Metalloproteinases, and p53 in Rat and Human Cholangiocarcinoma. Ann Surg, 240(1), 89–94. doi: 10.1097/01.sla.0000129492.95311.f2.

Kim, H. J., Kim, J. S., Kang, C. D., Lee, S. J., Kim, J. Y., Yeon, J. E., et al. (2005). Expression of epidermal growth factor receptor, ErbB2 and matrix metalloproteinase-9 in hepatolithiasis and cholangiocarcinoma. Korean J Gastroenterol., 45(1), 52–59.

Rasband, W. S. & Image J. U. S. National Institutes of Health, Bethesda, Maryland, USA Retrieved from http://imagej.nih.gov/ij/, 1997–2012.

Ishii, Y., Nakasato, Y., Kobayashi, S., Yamazaki, Y., & Aoki, T. (2003) A Study on Angiogenesis-Related Matrix Metalloproteinase Networks in Primary Hepatocellular Carcinoma. J. Exp. Clin. Cancer Res., 22(3), 461–470.

Yan, Zhang, Yucheng, Shen, Bin, Cao, Aiting, Yan, & Haoming, Ji (2015) Elevated expression levels of androgen receptors and matrix metalloproteinase-2 and -9 in 30 cases of hepatocellular carcinoma compared with adjacent tissues as predictors of cancer invasion and staging. Experimental and therapeutic medicine, 9(3), 905–908.

Nart, D., Yaman, B., Yılmaz, F., Zeytunlu, M., Karasu, Z., Kılıc, M. (2010) Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantation. J Liver Transplantation, 16(5), 621–630. doi: 10.1002/lt.22028.

McKenna, G. J., Chen, Y., Smith, R. M., Meneghetti, A., Ong, C., McMaster, R. et al. (2002) A role for matrix metalloproteinases and tumor host interaction in hepatocellular carcinomas. Am J Surg., 183(5), 588–594. doi: 10.1016/S0002-9610(02)00833-4.

Jiang, Y. F., Yang, Z. H., Hu, J. Q. (2000) Recurrence or metastasis of HCC: predictors, early detection and experimental antiangiogenic therapy. World J Gastroenterol, 6(1), 61–65.

Roeb, E., Bosserhoff, A.K., Hamacher, S., Jansen, B., Dahmen, J., Wagner, S. et al. (2005) Enhanced migration of tissue inhibitor of metalloproteinase overexpressing hepatoma cells is attributed to gelatinases: relevance to intracellular signaling pathways. World J Gastroenterol, 11, 1096–1104. doi: 10.3748/wjg.v11.i8.1096.

Matsumoto, E., Nakatsukasa, H., Nouso, K., Kobayashi, Y., Nakamura, S., Suzuki, M., et al. (2004) Increased levels of tissue inhibitor of metalloproteinase-1 in human hepatocellular carcinoma. Liver Int., 24(4), 379–383. doi: 10.1111/j.1478-3231.2004.0923.x.

Kutikhin, A. G., Natcheva, L. V., Magarill, Yu. A. (2009) Prognosticheskaya rol' i molekulyarno-biologicheskie aspekty formirovaniya kapsuly gepatocellyulyarnoj karcinomy: obzor literatury [Prognostic role and molecular-biological aspects of hcc capsule formation: review]. Sibirskij onkologicheskij zhurnal, 6(36), 70–77. [in Russian].

Joo, Y. E., Seo, Y. H., Lee, W. S., Kim, H. S., Choi, S.K., Rew, J.S., et al. (2000) Expression of Tissue Inhibitors of Metalloproteinases (TIMPs) in Hepatocellular Carcinoma. Korean J Intern Med, 15(3), 171–178.

Sawada, S., Murakami, K., Murata, J., Tsukada, K., & Saiki, I. (2001) Accumulation of extracellular matrix in the liver induces high metastatic potential of hepatocellular carcinoma to the lung. Int J Oncol, 19(1), 65–70. doi: 10.3892/ijo.19.1.65.

Shirabe, K., Shimada, M., Kajiyama, K., Hasegawa, H., Gion, T., Ikeda, Y., et al. (1999) Expression of matrix metalloproteinase-9 in surgically resected intrahepatic cholangiocarcinoma. Surgery, 126(5), 842–846.

Itatsu, K., Zen, Y., Yamaguchi, J., Ohira, S., Ishikawa, A., Ikeda, H., et al. (2008) Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts. Hum Pathol, 39(5), 710–719. doi: 10.1016/j.humpath.2007.09.016.

Qi, Sun, Chuanzong, Zhao1, Leizhou, Xia , Zhaobin, He , Zhihua, Lu , Chuan, Liu, et al. (2014) High expression of matrix metalloproteinase-9 indicates poor prognosis in human hilar cholangiocarcinoma. Int J Clin Exp Pathol, 7(9), 6157–6164.

How to Cite

1.
Tumanskiy VA, Zubko MD. Characteristics of the expression level of MMP-9 and TIMP-1 in hepatocellular and cholangiocellular liver carcinoma. Pathologia [Internet]. 2015May19 [cited 2024Apr.19];(1). Available from: http://pat.zsmu.edu.ua/article/view/42819

Issue

Section

Original research