Melanosis coli as a factor in the development of colorectal cancer

Melanosis coli is characteristic of patients with a long history of constipation and the use of laxatives – anthraquinone derivatives, which are quite prescribed by doctors and patients independently. As a rule, melanosis develops after 4–9 months of taking drugs from this group and is most common in women in the older age group. Pathogenetically, melanosis is characterized by the deposition of pigment in the lamina propria of the mucous membrane, manifested by a pronounced dark coloration of the mucosa, depending on the degree of pigmentation of the colon, melanosis is divided into three degrees. The most common localization is in the right colon, but cases with the spread of pigmentation to the left colon and other parts have been described. Diagnosis does not cause difficulties, melanosis coli is detected during routine endoscopic examination, and is confirmed by pathomorphological examination. Melanosis is an actual problem in terms of the risk of developing colorectal cancer (CRC). There are already convincing data proving that the frequency of detection of adenomas increases not only due to the absence of pigment accumulation by them, but also the pathogenetic aspects of the influence of melanosis on the occurrence and development of adenomas have been described. Proteomic analysis allows to determine the expression of various proteins, which confirms the role of melanosis in the development of colorectal cancer. It is also interesting to note that sometimes there are some difficulties in the differential diagnosis of melanosis, for example, with ischemic lesions of the colon. Patients with melanosis coli require close attention, timely diagnosis and treatment.

1. Van Gorkom B.A., de Vries E.G., Karrenbeld A., Kleibeuker J.H. Review article: anthranoid laxatives and their potential carcinogenic effects. Aliment Pharmacol Ther. 1999;13(4):443– 452. https://doi.org/10.1046/j.1365-2036.1999.00468.x.

2. Liu Z.H., Foo D.C.C., Law W.L., Chan F.S.Y., Fan J.K.M., Peng J.S. Melanosis coli: Harmless pigmentation? A case-control retrospective study of 657 cases. PLoS ONE. 2017;12(10):e0186668. https://doi.org/10.1371/journal.pone.0186668.

3. Nusko G., Schneider B., Ernst H., Wittekind C., Hahn E.G. Melanosis coli – a harmless pigmentation or a precancerous condition? Z Gastroenterol. 1997;35(5):313–318. Available at: https://pubmed.ncbi.nlm.nih.gov/9188145.

4. Abu Baker F., Mari A., Feldman D., Suki M., Gal O., Kopelman Y. Melanosis Coli: A Helpful Contrast Effect or a Harmful Pigmentation? Clin Med Insights Gastroenterol. 2018;11:1179552218817321. https://doi.org/10.1177/1179552218817321.

5. Nesheiwat Z., Al Nasser Y. Melanosis Coli. Treasure Island (FL): StatPearls Publishing; 2019. Available at: https://www.ncbi.nlm.nih.gov/books/NBK493146.

6. Siegers C.P., von Hertzberg-Lottin E., Otte M., Schneider B. Anthranoid laxative abuse – a risk for colorectal cancer? Gut. 1993;34(8):1099–1101. https://doi.org/10.1136/gut.34.8.1099.

7. Ghadially F.N., Walley V.M. Melanoses of the gastrointestinal tract. Histopathology. 1994;25(3):197–207. https://doi.org/10.1111/j.1365-2559.1994.tb01319.x.

8. Freeman H.J., Lotan R., Kim Y.S. Application of lectins for detection of goblet cell glycoconjugate differences in proximal and distal colon of the rat. Lab Invest. 1980;42(4):405–412. Available at: https://pubmed.ncbi.nlm.nih.gov/7374105.

9. Benavides S.H., Morgante P.E., Monserrat A.J., Zárate J., Porta E.A. The pigment of melanosis coli: a lectin histochemical study. Gastrointest Endosc. 1997;46(2):131–138. https://doi.org/10.1016/s0016-5107(97)70060-9.

10. Won K.H., Ramchand S. Melanosis of the ileum. Case report and electron microscopic study. Am J Dig Dis. 1970;15(1):57–64. https://doi.org/10.1007/BF02239347.

11. Almeida N., Figueiredo P., Lopes S., Freire P., Sousa V., Lérias C. et al. Small bowel pseudomelanosis and oral iron therapy. Dig Endosc. 2009;21(2):128–130. https://doi.org/10.1111/j.1443-1661.2009.00834.x.

12. Kim J., Hwang J.K., Choi W.S., Lee B.J., Park J.J., Kim J.S. et al. Pseudomelanosis ilei associated with ingestion of charcoal: case report and review of literature. Dig Endosc. 2010;22(1): 56–58. https://doi.org/10.1111/j.1443-1661.2009.00919.x.

13. Yen H.H., Chen Y.Y., Soon M.S. Pseudomelanosis duodeni: an unusual finding from upper gastrointestinal endoscopy. Clin Gastroenterol Hepatol. 2009;7(11):e68. https://doi.org/10.1016/j.cgh.2009.07.028.

14. Zhang L., Gao F. New progress of melanosis coli. Chin J Gastroenterol Hepatol. 2015;24(3):257–259.

15. Citronberg J., Kantor E.D., Potter J.D., White E. A prospective study of the effect of bowel movement frequency, constipation, and laxative use on colorectal cancer risk. Am J Gastroenterol. 2014;109(10):1640–1649. https://doi.org/10.1038/ajg.2014.233.

16. Nusko G., Schneider B., Schneider I., Wittekind C., Hahn E.G. Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study. Gut. 2000;46(5):651–655. https://doi.org/10.1136/gut.46.5.651.

17. Wang Z.C., Gao J., Zi S.M., Yang M., Du P., Cui L. Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli. J Dig Dis. 2013;14(8):417–424. https://doi.org/10.1111/1751-2980.12060.

18. Yoshimoto A.N., Bernardazzi C., Carneiro A.J., Elia C.C., Martinusso C.A., Ventura G.M. et al. Hedgehog pathway signaling regulates human colon carcinoma HT-29 epithelial cell line apoptosis and cytokine secretion. PLoS ONE. 2012;7(9):e45332. https://doi.org/10.1371/journal.pone.0045332.

19. Ma J., Tian L., Cheng J., Chen Z., Xu B., Wang L. et al. Sonic hedgehog signaling pathway supports cancer cell growth during cancer radiotherapy. PLoS ONE. 2013;8(6):e65032. https://doi.org/10.1371/journal.pone.0065032.

20. Zhu J., Liu C., Liu F., Wang Y., Zhu M. Knockdown of PFTAIRE Protein Kinase 1 (PFTK1) Inhibits Proliferation, Invasion, and EMT in Colon Cancer Cells. Oncol Res. 2016;24(3):137–144. https://doi.org/10.3727/096504016X14611963142218.

21. Monks T.J., Hanzlik R.P., Cohen G.M., Ross D., Graham D.G. Quinone chemistry and toxicity. Toxicol Appl Pharmacol. 1992;112(1):2–16. https://doi.org/10.1016/0041-008x(92)90273-u.

22. Sendelbach L.E. A review of the toxicity and carcinogenicity of anthraquinone derivatives. Toxicology. 1989;57(3):227–240. https://doi.org/10.1016/0300-483x(89)90113-3.

23. Biernacka-Wawrzonek D., Stępka M., Tomaszewska A., EhrmannJóśko A., Chojnowska N., Zemlak M., Muszyński J. Melanosis coli in patients with colon cancer. Prz Gastroenterol. 2017;12(1): 22–27. https://doi.org/10.5114/pg.2016.64844.

24. Sonnenberg A., Müller A.D. Constipation and cathartics as risk factors of colorectal cancer: a meta-analysis. Pharmacology. 1993;47(1 Suppl.):224–233. https://doi.org/10.1159/000139862.

25. Zhang X., Wu K., Cho E., Ma J., Chan A.T., Gao X. et al. Prospective cohort studies of bowel movement frequency and laxative use and colorectal cancer incidence in US women and men. Cancer Causes Control. 2013;24(5):1015–1024. https://doi.org/10.1007/s10552-013-0176-2.

26. Yang Z.Y., Jiang H., Qu Y., Wei M., Yan M., Zhu Z.G. et al. Metallopanstimulin-1 regulates invasion and migration of gastric cancer cells partially through integrin β4. Carcinogenesis. 2013;34(12):2851–2860. https://doi.org/10.1093/carcin/bgt226.

27. Dai Y., Pierson S., Dudney C., Zeng Y., Macleod V., Shaughnessy J.D., Stack B.C. Jr. Ribosomal protein metallopanstimulin-1 impairs multiple myeloma CAG cells growth and inhibits fibroblast growth factor receptor 3. Clin Lymphoma Myeloma Leuk. 2011;11(6):490–497. https://doi.org/10.1016/j.clml.2011.06.015.

28. Wang Z.C., Gao J., Zi S.M., Yang M., Du P., Cui L. Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli. J Dig Dis. 2013;14(8):417–424. https://doi.org/10.1111/1751-2980.12060.

29. Zolg W. The proteomic search for diagnostic biomarkers: lost in translation? Mol Cell Proteomics. 2006;5(10):1720–1726. https://doi.org/10.1074/mcp.R600001-MCP200.

30. Bartkowiak K., Wieczorek M., Buck F., Harder S., Moldenhauer J., Effenberger K.E. et al. Two-dimensional differential gel electrophoresis of a cell line derived from a breast cancer micrometastasis revealed a stem/ progenitor cell protein profile. J Proteome Res. 2009;8(4):2004–2014. https://doi.org/10.1021/pr8009758.

31. Makino T., Yamasaki M., Takeno A., Shirakawa M., Miyata H., Takiguchi S. et al. Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer. 2009;101(8):1298–1306. https://doi.org/10.1038/sj.bjc.6605313.

32. Ricciuti B., Leone M.C., Metro G. Melanosis coli or ischaemic colitis? That is the question. BMJ Case Rep. 2015; bcr2015212404. https://doi.org/10.1136/bcr-2015-212404.

33. Liu F., Chen Z., Wang J., Shao X., Cui Z., Yang C. et al. Overexpression of cell surface cytokeratin 8 in multidrugresistant MCF-7/MX cells enhances cell adhesion to the extracellular matrix. Neoplasia. 2008;10(11):1275–1284. https://doi.org/10.1593/neo.08810.

34. Wang J.F., Guo Z., Tang L., Guo J.S., Hu J., Liu J.Z. Prognostic associations of preoperative plasma levels of fibrinogen and D-dimer after curative resection in patients with colorectal cancer. Zhonghua Yi Xue Za Zhi. 2013;93(12):906–909. (In Chinese). https://doi.org/10.3760/cma.j.issn.0376-2491.2013.12.007.

35. Zhou X., Wang P., Zhang Y.J., Xu J.J., Zhang L.M., Zhu L. et al. Comparative proteomic analysis of melanosis coli with colon cancer. Oncol Rep. 2016;36(6):3700–3706. https://doi.org/10.3892/or.2016.5178.

36. Moeller J., Solomon R., Kiffin C., Ditchek J.J., Davare D.L. Melanosis Coli: A Case of Mistaken Identity-A Case Report. Perm J. 2019;23:18–063. https://doi.org/10.7812/TPP/18-063.

37. Chaudhary B.N., Sharma H., Nadeem M., Niayesh M.H. Ischemic colitis or melanosis coli: a case report. World J Emerg Surg. 2007;2:25. https://doi.org/10.1186/1749-7922-2-25.

38. Chan A.O., Leung G., Tong T., Wong N.Y. Increasing dietary fiber intake in terms of kiwifruit improves constipation in Chinese patients. World J Gastroenterol. 2007;13(35):4771–4775. https://doi.org/10.3748/wjg.v13.i35.4771.

39. Iovino P., Chiarioni G., Bilancio G., Cirillo M., Mekjavic I.B., Pisot R., Ciacci C. New onset of constipation during long-term physical inactivity: a proof-of-concept study on the immobilityinduced bowel changes. PLoS ONE. 2013;8(8):e72608. https:// doi.org/10.1371/journal.pone.0072608.

40. Doll R., Hostoffer R. Disappearance of Melanosis Coli After Administration of IVIG. Am J Gastroenterol. 2017;112(3):517– 518. https://doi.org/10.1038/ajg.2016.567.

41. Sun J.W., Gu J.N., Du P., Chen W. Comparison of two types of colectomy in treating slow transit constipation with or without melanosis coli. World J Gastroenterol. 2015;21(33):9736–9740. https://doi.org/10.3748/wjg.v21.i33.9736