Study of the expression of intestinal mucin MUC-2 and the marker of proliferative activity Ki-67 in colorectal carcinomas
Keywords:
colorectal cancer, digital morphometry, MUC-2, Ki-67.Abstract
Introduction. Colorectal carcinomas (CRCs), as defined by WHO, are malignant epithelial tumors originating in the large intestine, showing glandular or mucinous features of differentiation. The development of CRC demonstrates a complex pathogenesis due to a violation of the intestinal mucosal barrier. Goblet cells are thought to secrete mucin, which forms a mucosal barrier and maintains intestinal integrity. Mucin type 2 (MUC-2) is mainly expressed in the small and large intestine, and disturbances in its production are associated with various inflammatory diseases and carcinomas. Chronic inflammation leads to cell damage that transforms the inflamed epithelium into low-grade dysplasia, high-grade dysplasia, and further into CRC. Also, the literature emphasizes the importance of studying MUC-2 in individual histological types of CRC, which have a different course and prognosis for patient survival. The aim of the study was to evaluate the prognostic significance of the expression of intestinal mucin MUC-2 depending on the clinical and morphological characteristics and proliferative activity of colorectal carcinomas. Methods. The work examined the clinical and anatomical material of CRC of 37 patients (15 women and 22 men), which was obtained during operations (right hemicolectomy, resection of the sigmoid colon, Hartmann's operation, resection of the transverse colon, resection of the ileum); all of them were treated in the 2nd surgical department of the Dnipropetrovsk Regional Clinical Hospital in the period from 2019 to 2021. The age of the patients ranged from 27 to 82 years; the average age was 61.43±14.90 years. Primary monoclonal antibodies to Ki-67 (sp6, 1:250), MUC2 (sp1, RTU) and UltraVision Quanto imaging system, LabVision) were used for immunohistochemical examination. Results. The average intensity of MUC-2 staining showed a significant difference in individual histological types of CRC (the darkest staining was found in mucinous and ring-shaped cell carcinomas, the lightest in micropapillary adenocarcinoma, p<0.05); and also, in subgroups with different proliferative potential according to Ki-67 (a decrease in the intensity of MUC-2 expression was accompanied by an increase in the proliferation index, p<0.05). The distribution of MUC-2 expression variants – typical (membrane diffuse or membrane focal) or aberrant (cytoplasmic, cytoplasmic-nuclear dot like) showed a significant difference in the age group (with increasing age, the relative number of aberrant MUC-2 expression increased, p<0 .05); and also, in the group with G2, the relative number of aberrant MUC-2 expression was significantly higher compared to G3 (p<0.05). The absolute absence of an aberrant MUC-2 expression variant was noted in the group of CRC with metastases, compared to the group without metastases, where they were found in 50.00% (10 out of 20); in the group of CRC with a low proliferation index, compared to the groups of moderate and high proliferation, where they were found in 46.15% (6 out of 13) and 28.57% (4 out of 14), respectively; in certain histological types of CRC, namely, mucinous, ring-shaped cell and adenocarcinoma of the adenoma-like type. The largest number of aberrant variants of MUC-2 expression was observed in such histological types of CRC as medullary carcinoma 66.67% (2 of 3), micropapillary carcinoma 33.33% (1 of 3) and adenocarcinoma NOS 31.58% (6 of 19).
References
- Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Scientific Reports. 2020;71(3):209-249. https://doi.org/10.3322/caac.21660.
- Heather NM, Ward A, Jenab M, et al. Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study. Clinical Gastroenterology and Hepatology. 2019;17(7):1323-1331.e6. https://doi.org/10.1016/j.cgh.2018.07.030.
- Hofseth LJ, Hebert JR, Chanda A, et al. Early-onset colorectal cancer: initial clues and current views. Nature Reviews Gastroenterology & Hepatology volume. 2020;17:352-364. https://doi.org/10.1038/s41575-019-0253-4.
- Graff RE, Möller S, Passarelli MN, et al. Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer. Clinical Gastroenterology and Hepatology. 2017;15(8):1256-1264. https://doi.org/10.1016/j.cgh.2016.12.041.
- Johnson CM, Wei C, Ensor JE, et al. Meta-analyses of colorectal cancer risk factors. Cancer Causes Control. 2013;24:1207-1222. https://doi.org/10.1007/s10552-013-0201-5.
- Fedorenko ZP, Hulak LO, Mykhailovych YuY, et al. [Cancer in Ukraine, 2019-2020. Morbidity, mortality, performance indicators of the oncology service]. Bulletin of the National Chancery Register of Ukraine. 2021;22. Ukrainian.http://www.ncru.inf.ua/publications/BULL_22/.
- Zhang Q, Wu J, Bai X, Liang T. Evaluation of Intra-Tumoral Vascularization in Hepatocellular Carcinomas. Front. Med. 2020;7:584250. doi: 10.3389/fmed.2020.584250.
- Melling N, Kowitz CM, Simon R, et al. High Ki67 expression is an independent good prognostic marker in colorectal cancer. J Clin Pathol. 2016;69:209-214. https://doi:10.1136/jclinpath-2015-202985.
- Poslavska OV, Shponka IC, Hrytsenko PO. [Characteristics of the colorectal phenotype of carcinomas of unknown primary localization]. Journal of the Ukrainian Medical Stomatological Academy "Actual problems of pediatric medicine". 2018;18(3):111-115. Ukrainian.
- Ma YL, Peng JY, Zhang P, et al. Immunohistochemical analysis revealed CD34 and Ki67 protein expression as significant prognostic factors in colorectal cancer. Med Oncol. 2010; 27:304-309. https://doi.org/10.1007/s12032-009-9210-3.
- Gundamaraju R, Chong WC. Consequence of distinctive expression of MUC2 in colorectal cancers: How much is actually bad? Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2021;1876(1):188579. https://doi.org/10.1016/j.bbcan.2021.188579.
- Chao L, Didi Z, Libin Y, et al. Prognostic Value of MUC2 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis. Gastroenterology Research and Practice. 2018;2018:12 https://doi.org/10.1155/2018/6986870.
- Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nature Methods. 2012;9(7):676-682. doi:10.1038/nmeth.2019.
- Poslavska OV. [The methodology of using software for the analysis of digital photomicrographs based on the course of pathomorphology in order to improve the professional level of students and scientists]. Morphology. 2015;9(3):122-126. Ukrainian.
- Poslavska OV. [Determining the linear dimensions and areas of individual morphological objects on photomicrographs using the ImageJ program. Morphology]. 2016;10(3):377-381. Ukrainian.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world.
The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.
