urmjУральский медицинский журналUral Medical Journal2949-4389Ural State Medical Universityurmj-66Research ArticleОНКОМОРФОЛОГИЯИммуногистохимическая характеристика экспрессии Ki67 в предопухолевых образованиях толстой кишкиImmunohistochemical characteristics of Ki67 expression in premalignant lesions of the colon and rectumХарловаОльга АндреевнаKharlovaO. A.olga.arsenteva@gmail.comОлейниковаН. А.OleynikovaN. A.noemail@neicon.ruМальковП. Г.MalkovP. G.noemail@neicon.ruДаниловаН. В.DanilovaN. V.noemail@neicon.ruФГБУ ВО Московский государственный университет имени М. В. ЛомоносоваRussian Federation201814042021026269Copyright © Харлова О.А., Олейникова Н.А., Мальков П.Г., Данилова Н.В., 20212021Харлова О.А., Олейникова Н.А., Мальков П.Г., Данилова Н.В.Kharlova O.A., Oleynikova N.A., Malkov P.G., Danilova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.umjusmu.ru/jour/article/view/66

Введение. Согласно классификации Воз 2010 года предшественниками колоректального рака являются классические аденомы (тубулярные - АТ, тубуло-ворсинчатые - ATV и ворсинчатые) и зубчатые образования (гиперпластические полипы - НР, зубчатые аденомы/полипы на широком основании - SSA/P, традиционные зубчатые аденомы - TSA). определение экспрессии Ki67 является одним из компонентов оценки потенциала злокачественности предопухолевых образований толстой кишки. Материалы и методы. Проведена оценка иммуногистохимической экспрессии Ki67 в 28 НР, 30 SSA/P, 15 TSA, 30 АТ, 28 ATV. Во всех случаях оценивался средний процент и локализация окрашенных ядер. Результаты. В НР и SSA/P экспрессия Ki67 отмечена преимущественно в нижних отделах крипт, индекс Ki67 в НР составил 63%, в нерасширенных криптах SSA/P - 66,2% (р>0,05). В расширенных криптах SSA/P индекс Ki67 составил 35,8%, что достоверно ниже, чем в НР и нерасширенных криптах SSA/P (р<0,05). В АТ, ATV и TSA экспрессия Ki67 отмечена преимущественно в верхних отделах крипт и составляет 59,3%, 64,2% и 63% соответственно (р>0,05). В эктопических криптах TSA индекс Ki67 составляет 29,9% и достоверно не отличается от базальных отделов крипт ATV. Выводы. Преобладание Ю67-позитивных клеток в верхней половине крипт свидетельствуют в пользу «нисходящей» модели развития рака в АТ, ATV и TSA; преобладание Ki67-позитивных клеток в нижней половине крипт в НР и SSA/P может свидетельствовать в пользу «восходящей» модели канцерогенеза. На основании преимущественной локализации Ki67-позитивных клеток и индекса пролиферативной активности можно разделить предопухолевые образования толстой кишки на две группы - зубчатые образования (НР + SSA/P) и классические аденомы (АТ + ATV + TSA).

Introduction. According to the 2010 WHO classification, the precursors of colorectal cancer are conventional adenomas (tubular -AT, tubulo-villous - ATV and villous) and serrated lesions (hyperplastic polyps - HP, sessile serrated adenomas/polyps - SSA/P, traditional serrated adenomas - TSA). The evaluation of Ki67 expression is one of the components of the malignant potential of premalignant lesions of the colon and rectum. Materials and methods. Immunohistochemical expression of Ki67 was assessed in 28 HP, 30 SSA/P, 15 TSA, 30 AT, 28 ATV. In all cases the average percentage and location of colored nuclei were estimated. Results. Ki67 expression in HP and SSA/P was predominantly registered in the lower crypt regions, the Ki67-index in HP was 63%, in the non-dilated crypts of SSA/P - 66,2% (p>0,05). In the dilated crypts of SSA/P the Ki67-index was 35,8%, that is significantly lower than in the HP and the non-dilated crypts of SSA/P (p<0,05). In AT, ATV and TSA, the expression of Ki67 is noted predominantly in the upper crypt regions and is 59,3%, 64,2% and 63%, respectively (p>0,05). In the ectopic crypts of TSA the Ki67-index is 29,9% and is not significantly different from the basal regions in ATV. Conclusion. The predominance of Ki67-positive cells in the upper half of the crypts supports the "descending" model of cancer development in AT, ATV and TSA; the predominance of Ki67-positive cells in the lower half of the crypts in HP and SSA/P may be indicative of the "ascending" model of carcinogenesis. Based on the predominant localization of Ki67-positive cells and the index of proliferative activity, it is possible to divide the premalignant lesions of the colon and rectum into two groups: serrated lesions (HP + SSA/P) and conventional adenomas (AT + ATV + TSA).

классические аденомызубчатые образованияэкспрессия Ki67потенциал злокачественностиconventional adenomasserrated lesionsKi67 expressionmalignant potentialReferencesAbdelzaher E., Rizk A. M., Bessa S. S., Omer K. M. Predictive value of immunohistochemical expression of claudin-1 in colonic carcinoma. Journal of the Egyptian National Cancer Institute. 2011;23(4):123-31.Abdelzaher E., Rizk A. M., Bessa S. S., Omer K. M. Predictive value of immunohistochemical expression of claudin-1 in colonic carcinoma. Journal of the Egyptian National Cancer Institute. 2011;23(4):123-31.He E. Y., Wyld L., Sloane M. A., Canfell K., Ward R. L. The molecular characteristics of colonic neoplasms in serrated polyposis: a systematic review and metaanalysis. The journal of pathology Clinical research. 2016;2(3):127-37.He E. Y., Wyld L., Sloane M. A., Canfell K., Ward R. L. The molecular characteristics of colonic neoplasms in serrated polyposis: a systematic review and metaanalysis. The journal of pathology Clinical research. 2016;2(3):127-37.Snover D. C., Ahnen D. J., Burt R. W., Odze R. D. Serrated polyps of the colon and rectum and serrated polyposis. In: Bosman F. T., Carneiro F., Hruban R. H., Theise N. D., editor. WHO classification of tumors Pathology and genetics Tumors of the digestive system. 4 ed. Berlin: Springer-Verlag; 2010. p. 160-5.Snover D. C., Ahnen D. J., Burt R. W., Odze R. D. Serrated polyps of the colon and rectum and serrated polyposis. In: Bosman F. T., Carneiro F., Hruban R. H., Theise N. D., editor. WHO classification of tumors Pathology and genetics Tumors of the digestive system. 4 ed. Berlin: Springer-Verlag; 2010. p. 160-5.Puglisi M. A., Tesori V., Lattanzi W., Gasbarrini G. B., Gasbarrini A. Colon cancer stem cells: controversies and perspectives. World J Gastroenterol. 2013;19(20):2997-3006.Puglisi M. A., Tesori V., Lattanzi W., Gasbarrini G. B., Gasbarrini A. Colon cancer stem cells: controversies and perspectives. World J Gastroenterol. 2013;19(20):2997-3006.Barker N., Ridgway R.A., van Es J. H., et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457(7229):608-11.Barker N., Ridgway R.A., van Es J. H., et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457(7229):608-11.Shih I. M., Wang T. L., Traverso G., et al. Top-down morphogenesis of colorectal tumors. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(5):2640-5.Shih I. M., Wang T. L., Traverso G., et al. Top-down morphogenesis of colorectal tumors. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(5):2640-5.Sobecki M., Mrouj K., Colinge J., et al. Cell-Cycle Regulation Accounts for Variability in Ki-67 Expression Levels. Cancer research. 2017;77(10):2722-34.Sobecki M., Mrouj K., Colinge J., et al. Cell-Cycle Regulation Accounts for Variability in Ki-67 Expression Levels. Cancer research. 2017;77(10):2722-34.Sobecki M., Mrouj K., Camasses A., et al. The cell proliferation antigen Ki-67 organises heterochromatin. eLife. 2016;5.Sobecki M., Mrouj K., Camasses A., et al. The cell proliferation antigen Ki-67 organises heterochromatin. eLife. 2016;5.Mogoanta S. S., Vasile I., Totolici B., et al. Colorectal cancer - clinical and morphological aspects. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2014;55(1):103-10.Mogoanta S. S., Vasile I., Totolici B., et al. Colorectal cancer - clinical and morphological aspects. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2014;55(1):103-10.Baker A. M., Graham T. A., Elia G., Wright N. A., Rodriguez-Justo M. Characterization of LGR5 stem cells in colorectal adenomas and carcinomas. Scientific reports. 2015;5:8654.Baker A. M., Graham T. A., Elia G., Wright N. A., Rodriguez-Justo M. Characterization of LGR5 stem cells in colorectal adenomas and carcinomas. Scientific reports. 2015;5:8654.Jiao Y. F., Nakamura S., Sugai T., Yamada N., Habano W. Serrated adenoma of the colorectum undergoes a proliferation versus differentiation process: new conceptual interpretation of morphogenesis. Oncology. 2008;74(3-4):127-34.Jiao Y. F., Nakamura S., Sugai T., Yamada N., Habano W. Serrated adenoma of the colorectum undergoes a proliferation versus differentiation process: new conceptual interpretation of morphogenesis. Oncology. 2008;74(3-4):127-34.Baretton G. B., Diebold J., Christoforis G., et al. Apoptosis and immunohistochemical bcl-2 expression in colorectal adenomas and carcinomas. Aspects of carcinogenesis and prognostic significance. Cancer. 1996;77(2):255-64.Baretton G. B., Diebold J., Christoforis G., et al. Apoptosis and immunohistochemical bcl-2 expression in colorectal adenomas and carcinomas. Aspects of carcinogenesis and prognostic significance. Cancer. 1996;77(2):255-64.Fujimori Y., Fujimori T., Imura J., et al. An assessment of the diagnostic criteria for sessile serrated adenoma/ polyps: SSA/Ps using image processing software analysis for Ki67 immunohistochemistry. Diagnostic pathology. 2012;7:59.Fujimori Y., Fujimori T., Imura J., et al. An assessment of the diagnostic criteria for sessile serrated adenoma/ polyps: SSA/Ps using image processing software analysis for Ki67 immunohistochemistry. Diagnostic pathology. 2012;7:59.Snover D. C., Batts K. P. Serrated Colorectal Neoplasia. Surgical Pathology Clinics. 2010;3(2):207-40.Snover D. C., Batts K. P. Serrated Colorectal Neoplasia. Surgical Pathology Clinics. 2010;3(2):207-40.Torlakovic E. E., Gomez J. D., Driman D. K., et al. Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA). The American journal of surgical pathology. 2008;32(1):21-9.Torlakovic E. E., Gomez J. D., Driman D. K., et al. Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA). The American journal of surgical pathology. 2008;32(1):21-9.Bettington M. L., Walker N. I., Rosty C., et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2015;28(3):414-27.Bettington M. L., Walker N. I., Rosty C., et al. A clinicopathological and molecular analysis of 200 traditional serrated adenomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2015;28(3):414-27.Su T., Washington M. K., Ness R. M., et al. Comparison of biomarker expression between proximal and distal colorectal adenomas: The Tennessee-Indiana adenoma recurrence study. Molecular carcinogenesis. 2016.Su T., Washington M. K., Ness R. M., et al. Comparison of biomarker expression between proximal and distal colorectal adenomas: The Tennessee-Indiana adenoma recurrence study. Molecular carcinogenesis. 2016.Lash R. H., Genta R. M., Schuler C. M. Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients. Journal of clinical pathology. 2010;63(8):681-6.Lash R. H., Genta R. M., Schuler C. M. Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients. Journal of clinical pathology. 2010;63(8):681-6.Wang L. P., Chen J., Ning H. Y., et al. [Serrated lesions of colon and their malignant potential]. Zhonghua bing li xue za zhi = Chinese journal of pathology. 2010;39(7):447-51.Wang L. P., Chen J., Ning H. Y., et al. [Serrated lesions of colon and their malignant potential]. Zhonghua bing li xue za zhi = Chinese journal of pathology. 2010;39(7):447-51.

The authors declare that there are no conflicts of interest present.