Abstract
Aim. In order to determine the level of immunohistochemical expression of E-cadherin and β-catenin in hepatocellular and cholangiocellular liver cancer of different diameters and areas of the immunopositive cells trephine biopsies of liver of 94 patients were studied, among them 55 (58.51%) had hepatocellular carcinoma (HCC) and 39 (41.49%) had cholangiocellular liver cancer (CCC).Methods and results. Considering the size of the tumor determined by ultrasound examination of the liver 21 HCC and 17 CCC less than5 cmin diameter, and 34 HCC and 22 CCC with diameter more than 5 cm were assayed. The expression of E-cadherin by cells was determined using a monoclonal antibody Mo-Hu E -Cadherin, Clone NCH-38, and the expression of β-catenin - using monoclonal antibodies Mo a Hu Beta-Catenin, Clone E247 s-Catenin-1. The level of expression of immunohistochemical markers of tumor cells and immunopositive tumor cells area were determined by photo digital morphometry in digital image processing program Image J. It was found that in 63,64% of patients with HCC and 100% of patients with CCC, liver cancer cells show membrane or membrane-cytoplasmic expression of E-cadherin. E-cadherin immunopositive cells make up 42,25±15,12% of area of HCC tissue section and 35,13±15,69% of area of liver tissue section of CCC. In the 94,55% of HCC cases and 100% of patients with CCC membrane expression of β-catenin, combined with a nuclear or cytoplasmic expression of the protein, was revealed in tumor cells. β-catenin immunopositive cells make up 62,39±20,41% of area of HCC tissue section and 55,83±19,67% of area of liver tissue section in CCC. In HCC and CCC, between low expression of E-cadherin by tumor cells and high levels of β-catenin a direct strong correlation is observed. In large HCC and CCC compared with smaller tumors up to5 cmin diameter, significantly smaller space was occupied by E-cadherin-immunopositive cells and larger area was occupied by β-catenin-immunopositive cells.Conclusion. The comparison of the expression of adhesively-migration markers by tumor cells shows that hepatocellular carcinoma and cholangiocellular cancer are characterized by early loss of intercellular adhesion bonds and high potencies to invasive growth in the liver.
Highlights
С целью определения уровня иммуногистохимической экспрессии E-кадгерина и β-катенина в гепатоцеллюлярном и холангиоцеллюлярном раке печени разного диаметра, а также площади иммунопозитивных клеток в этих опухолях исследованы трепанобиоптаты печени 94 больных, среди которых 55 (58,51%) пациентов страдали гепатоцеллюлярным раком (ГЦР) и 39 (41,49%) – холангиоцеллюлярным раком (ХЦР) печени
In order to determine the level of immunohistochemical expression of E-cadherin and β-catenin in hepatocellular and cholangiocellular liver cancer of different diameters and areas of the immunopositive cells trephine biopsies of liver of 94 patients were studied, among them 55 (58,51%) had hepatocellular carcinoma (HCC) and 39 (41,49%) had cholangiocellular liver cancer (CCC)
In the 94,55% of HCC cases and 100% of patients with CCC membrane expression of β-catenin, combined with a nuclear or cytoplasmic expression of the protein, was revealed in tumor cells. β-catenin immunopositive cells make up 62,39±20,41% of area of HCC tissue section and 55,83±19,67% of area of liver tissue section in CCC
Summary
The comparison of the expression of adhesively-migration markers by tumor cells shows that hepatocellular carcinoma and cholangiocellular cancer are characterized by early loss of intercellular adhesion bonds and high potencies to invasive growth in the liver. Результаты и их обсуждение Проведённые нами исследования показали, что в ткани здоровой печени пациентов контрольной группы мембранная экспрессия Е-кадгерина наблюдалась в 100% гепатоцитов, Е-кадгерин-иммунопозитивными были также все клетки, выстилающие желчевыводящие протоки печени. У пациентов контрольной группы в нормальной ткани печени во всех гепатоцитах печени наблюдался высокий (147,51±28,73 УЕОП) уровень цитоплазматически-мембранной экспрессии β-катенина, а также высокий (133,19±30,21 УЕОП) уровень цитоплазматически-мембранной экспрессии этого белка во всех эпителиальных клетках желчевыводящих протоков. При иммуногистохимическом анализе экспрессии Е-кадгерина клетками ГЦР получили результаты: у 36,36% больных экспрессия Е-кадгерина в опухолевых гепатоцитах ГЦР не выявлялась. При анализе экспрессии β-катенина установили, что у 94,55% больных в клетках ГЦР выявлялась экспрессия этого белка, у 5,45% больных отсутствовала экспрессия β-катенина в клетках ГЦР. Умеренный уровень экспрессии (73,25±15,12 УЕОП) Е-кадгерина клетками ХЦР печени определён у 30,77% пациентов, низкий уровень экспрессии Е-кадгерина (35,45±9,32 УЕОП) выявлен у 25,64% больных. Позитивная мембранная экспрессия Е-кадгерина и β-катенина была обнаружена ими в 37,8% и 41,94% наблюдений соответственно, в 16,13% наблюдений установлена ядерная экспрессия β-катенина
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