The expression of tumor progression markers in hepatocellular and cholangiocellular liver carcinomas of different sizes
DOI:
https://doi.org/10.14739/2409-2932.2015.2.46615Keywords:
Liver Neoplasms, Hepatocellular Cancer, Cholangiocarcinoma, Tumor MarkersAbstract
Aim. Histopathological and immunohistochemical study of trephine biopsy of the liver in 94 patients, including 55 patients who suffered from hepatocellular carcinoma (HCC) and 39 - cholangiocellular carcinoma (CCC) with various sizes determined by ultrasound of the liver were carried out.
Methods and results. The photo digital morphometry was used to estimate the area of immunopositive cells expressing Ki-67, p53, caspase-3, E-cadherin, β-catenin, MMP-9 and TІMR-1 in 21 HCC and 17 CCC up to5 cm in diameter and in 34 HCC and 22 CCC more than 5 cm in diameter. It is found that in HCC more than 5 cm diameter area of cells expressing p53, Ki-67, β-catenin and MMP-9 was significantly higher (2, 1.4, 1.8 and 1.6 times, respectively) than in the HCC with diameter less than 5 cm, and the area of E-cadherin-positive cells in the large tumors was 1.8 times less than in small ones. In the CCC with diameter greater than 5 cm area of cells expressing p53, Ki-67, β-catenin and MMP-9 was significantly higher (1.8, 1.4, 1.7 and 1.3 times, respectively) than in CCC with diameter less than 5 cm, and the area of the E-cadherin-positive cells in large tumor was two times less than in small tumors. According to the comparative analysis, in HCC and CCC of different diameters areas of caspase-3-positive and ТІМР-1-positive cells were not significantly different.
Conclusion. Thus, increasing size of HCC and CCC is accompanied by the overexpression of nuclear oncoprotein p53, increased levels of tumor cell proliferation, tumor cell loss of intercellular adhesion bonds and an increase in the expression of metalloproteinase-9, all of which contribute to the rapid aggressive and invasive growth of tumors in the liver.
References
Kolosov A.E. Rak pecheni i prognoz dlya bol'nyh / Kolosov A.E.,ZHuravlev V.A.- Sankt-Peterburg. – 2002. - 144 s.
Hirurgicheskoe lechenie pervichnogo raka pecheni/ [Patyutko YU.I., Sagajdak I.V., CHuchuev E.S. i dr. ]- Prakticheskaya onkologiya. - 2008. - №9(4). – S.197-201.
Maluccio M. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma/Maluccio M., Covey A. CA Cancer J Clin.- 2012.- V.62(6)-р. 394-399
Ioannou G.N. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival/ Ioannou G.N., Perkins J. D., Carithers R. L.- Gastroenterology.- 2008.- V.134(5)-р.1342-1351
Results of resection for hilar cholangiocarcinoma with analysis of prognostic factors/ Havlik R., Sbisa E., Tullo A. [et al.] // Hepatogastroenterology. - 2000. – V. 47(34). – р.927– 931.;
Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma/ [Jiang Chen , Jie Zhao, Rui Ma [et al.] // A Meta-Analysis /PLoS One. 2014.- V.9(8).-р.1-8.;
Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma / [Gao Z.H., Tretiakova M.S., Liu W.H [et al ] // Mod Pathol. – 2006. – V.19(4). – P.533-540.;
Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas / [Theret N., Musso O., Turlin B [et al. ] // Hepatology. – 2001. – V.34(1). – P.82-88.
Pat 99314 Ukraїna, MPK 2015.01 G01N 21/00 G06K 9/00 Sposіb fotocifrovoї morfometrії іmunogіstohіmіchnih preparatіv / Tumans'kij V.O., Єvsєєv A.V., Kovalenko І.S., Zubko M.D. – zayavnik і patentovlasnik Zaporіz'kij derzh. med. un-t.; zayavl. 29.12.14.; opubl. 25.05.15, Byul. №10.
Rasband W.S. ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA – http://imagej.nih.gov/ij/, 1997–2012.
Tumanskij V. A. Harakteristika urovnya ehkspressii MMR-9 i TIMP-1 v gepatocellyulyarnom i holangiocellyulyarnom rake pecheni/ Tumanskij V. A., Zubko M. D. - Patologіya.- 2015. - №1 (33). – S.20-25
Zubko M.D. Harakteristika urovnya ehkspressii E-kadgerina i β-katenina v gepatocellyulyarnom i holangiocellyulyarnom rake pecheni// Patologіya, 2015.- №2 (34), str.64-70
Lazarevich N.L. Molekulyarnye mekhanizmy progressii opuholej pecheni // Uspekhi biol. himii.- 2004. –T. 44. – str.365-418.;
Koskinas J., Petraki K., Kavantzas N. et al. Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma [Koskinas J., Petraki K., Kavantzas N. [et al.] // Viral Hepatitis. - 2005. - №12(6). - р. 635-641.;
Mutations of p53 tumor suppressor gene, apoptosis, and proliferation in intrahepatic cholangiocellular carcinoma of the liver [Tannapfel A., Weinans L., Geissler F[et al.].- Digestive Diseases and Sciences. – 2002. – V.45(2). – р.317–324.
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