Skip to main content

Advertisement

SpringerLink
Log in

Fibrosis and Mast Cells in Colorectal Lesions: Significance in Adenoma-Colorectal Cancer Sequence and Association with Diet

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Adenoma is the most common benign neoplasm with potential to progress into colorectal cancer (CRC), a disease responsible for high rates of mortality. However, it is not possible yet to establish which lesions will evolve into CRC. We aimed to investigate the intrinsic factors, diet profile, and microenvironment as factors involved in adenoma-CRC progression.

Methods

We evaluated nutritional profile and microscopic features. Adenomas and CRC lesions were stained with Mallory’s trichrome to reveal fibrosis and Alcian blue to identify mast cells.

Results

A total of 143 patients was selected, 66 % diagnosed with normal mucosa, 28.4 % with benign lesion, and 5.6 % with CRC. A higher frequency of lesions was associated with patients older than 50 years (26.57 %) and women (18.18 %), but men were more likely to develop CRC. Regarding microscopic aspects, epithelium-connective tissue interface with disorganization feature was significantly higher in CRC when compared to adenoma (P = 0.0007). A greater fibrosis around vessels was also observed in CRC (P = 0.01). The statistical analysis indicated a significant correlation between mast cell population and patients older than 50 years (P < 0.01), male (P < 0.01), with right colon lesion (P < 0.05) and CRC. Low consumption of leafy greens (P < 0.001) and carotenoids (P < 0.01) and elevated consumption of red meat (P < 0.001) were associated with a high density of mast cells.

Conclusions

An association between clinical, diet profile, and microscopic features in colorectal lesions was observed, with a progressive change in the microenvironment during adenoma-CRC sequence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CRC:

colorectal cancer

ECM:

extracellular matrix

DNA:

deoxyribonucleic acid

TNFα:

tumor necrosis factor alpha

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi:10.3322/caac.20107.

    Article  PubMed  Google Scholar 

  2. Mansouri D, McMillan DC, Grant Y, Crighton EM, Horgan PG. The impact of age, sex and socioeconomic deprivation on outcomes in a colorectal cancer screening programme. PLoS One. 2013;8(6):e66063. doi:10.1371/journal.pone.0066063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hjartåker A, Aagnes B, Robsahm TE, Langseth H, Bray F, Larsen IK. Subsite-specific dietary risk factors for colorectal cancer: a review of cohort studies. J Oncol. 2013;2013:1–14. doi:10.1155/2013/703854.

    Article  Google Scholar 

  4. Haas SL, Ye W, Löhr JM. Alcohol consumption and digestive tract cancer. Curr Opin Clin Nutr Metab Care. 2012;15(5):457–67. doi:10.1097/MCO.0b013e3283566699.

    Article  CAS  PubMed  Google Scholar 

  5. Koh WP, Nelson HH, Yuan JM, Van den Berg D, Jin A, Wang R, et al. Glutathione S-transferase (GST) gene polymorphisms, cigarette smoking and colorectal cancer risk among Chinese in Singapore. Carcinogenesis. 2011;32(10):1507–11. doi:10.1093/carcin/bgr175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Murphy N, Norat T, Ferrari P, Jenab M, Bueno-de-Mesquita B, Skeie G, et al. Dietary fiber intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC). PLoS One. 2012;7(6):e39361. doi:10.1371/journal.pone.0039361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E, et al. Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Ann Oncol. 2012;23(1):37–45. doi:10.1093/annonc/mdr269.

    Article  CAS  PubMed  Google Scholar 

  8. Burton AM, Hovick SR, Peterson SK. Health behaviors in patients and families with hereditary colorectal cancer. Clin Colon Rectal Surg. 2012;25(2):111–7. doi:10.1055/s-0032-1313782.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, et al. Matrix cross linking forces tumor progression by enhancing integrin signaling. Cell. 2009;139(5):891–906. doi:10.1016/j.cell.2009.10.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 2007;67(6):2649–56.

    Article  CAS  PubMed  Google Scholar 

  11. Zhao LW, Li C, Zhang RL, Xue HG, Zhang FX, Zhang F, et al. B7-H1 and B7-H4 expression in colorectal carcinoma: correlation with tumor FOXP3+ regulatory T-cell infiltration. Acta Histochem. 2014;116(7):1163–8. doi:10.1016/j.acthis.2014.06.003.

    Article  CAS  PubMed  Google Scholar 

  12. Ribatti D. Mast cells as therapeutic target in cancer. Eur J Pharmacol. 2015;S0014–2999(15):00356–8. doi:10.1016/j.ejphar.2015.02.056.

    Google Scholar 

  13. Midulla F, Tromba V, Lo Russo L, Mileto F, Sabatino G, Sgarrella M, et al. Cytokines in the nasal washes of children with respiratory syncytial virus bronchiolitis. Int J Immunopathol Pharmacol. 2006;19(1):231–5.

    CAS  PubMed  Google Scholar 

  14. Theoharides TC, Conti P. Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 2004;25(5):235–41.

    Article  CAS  PubMed  Google Scholar 

  15. Fisher ER, Sass R, Watkins G, Johal J, Fisher B. Tissue mast cells in breast cancer. Breast Cancer Res Treat. 1985;5(3):285–91.

    Article  CAS  PubMed  Google Scholar 

  16. Veen T, Stormark K, Nedrebø BS, Berg M, Søreide JA, Kørner H, et al. Long-term follow-up and survivorship after completing systematic surveillance in stage I–III colorectal cancer: who is still at risk? J Gastrointest Cancer. 2015;46(3):259–66. doi:10.1007/s12029-015-9723-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH, Mulrow CD, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997;112(2):594–642.

    Article  CAS  PubMed  Google Scholar 

  18. Meguid RA, Slidell MB, Wolfgang CL, Chang DC, Ahuja N. Is there a difference in survival between right- versus left-sided colon cancers? Ann Surg Oncol. 2008;15(9):2388–94. doi:10.1245/s10434-008-0015-y.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Paszek MJ, Weaver VM. The tension mounts: mechanics meets morphogenesis and malignancy. J Mammary Gland Biol Neoplasia. 2004;9(4):325–42.

    Article  PubMed  Google Scholar 

  20. Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell. 2005;8(3):241–54.

    Article  CAS  PubMed  Google Scholar 

  21. Higashi N, Ishii H, Fujiwara T, Morimoto-Tomita M, Irimura T. Redistribution of fibroblasts and macrophages as micrometastases develop into established liver metastases. Clin Exp Metastasis. 2002;19(7):631–8.

    Article  PubMed  Google Scholar 

  22. Ch’ng S, Wallis RA, Yuan L, Davis PF, Tan ST. Mast cells and cutaneous malignancies. Mod Pathol. 2006;19(1):149–59.

    Article  PubMed  Google Scholar 

  23. Yang Z, Zhang B, Li D, Lv M, Huang C, Shen GX, et al. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS One. 2010;5(1):e8922. doi:10.1371/journal.pone.0008922.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Malfettone A, Silvestris N, Saponaro C, Ranieri G, Russo A, Caruso S, et al. High density of tryptase-positive mast cells in human colorectal cancer: a poor prognostic factor related to protease-activated receptor 2 expression. J Cell Mol Med. 2013;17(8):1025–37. doi:10.1111/jcmm.12073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 1999;13(11):1382–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kim MS, Chae HJ, Shin TY, Kim HM, Kim HR. Estrogen regulates cytokine release in human mast cells. Immunopharmacol Immunotoxicol. 2001;23(4):495–504.

    Article  CAS  PubMed  Google Scholar 

  27. Mahay S, Pariente JA, Lajas AI, Adeghate E, Rolph CE, Singh J. Effects of ageing on morphology, amylase release, cytosolic Ca2+ signals and acyl lipids in isolated rat parotid gland tissue. Mol Cell Biochem. 2004;266(1-2):199–208.

    Article  CAS  PubMed  Google Scholar 

  28. Ishikawa S, Tamaki S, Ohata M, Arihara K, Itoh M. Heme induces DNA damage and hyperproliferation of colonic epithelial cells via hydrogen peroxide produced by hemeoxygenase: a possible mechanism of heme-induced colon cancer. Mol Nutr Food Res. 2010;54(8):1182–91. doi:10.1002/mnfr.200900348.

    CAS  PubMed  Google Scholar 

  29. Vergara-Castañeda HA, Guevara-González RG, Ramos-Gómez M, Reynoso-Camacho R, Guzmán-Maldonado H, Feregrino-Pérez AA, et al. Non-digestible fraction of cooked bean (Phaseolusvul- garis L.) cultivar Bayo Madero suppresses colonic aberrant crypt foci in azoxymethane-induced rats. Food Funct. 2010;1(3):294–300. doi:10.1039/c0fo00130a.

    Article  PubMed  Google Scholar 

  30. Campos-Vega R, Reynoso-Camacho R, Pedraza-Aboytes G, Acosta-Gallegos JA, Guzman-Maldonado SH, Paredes-Lopez O, et al. Chemical composition and in vitro polysaccharide fermentation of different beans (Phaseolus vulgaris L.). J Food Sci. 2009;74(7):T59–65. doi:10.1111/j.1750-3841.2009.01292.x.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Brazilian National Council for Scientific and Technological Development (CNPq) process number: 479694 2013-3 and the State of Espírito Santo Research Foundation (FAPES) process number: 67659870 006/2014. The funding sources did not participate in any part of this study.

The authors gratefully acknowledge Rossini Cipriano Gama, Vitória ApartHospital, Service of Coloproctology, which provided valuable help during the medical procuderes.

Author information

Authors and Affiliations

  1. Department of Morphology, Federal University of Espírito Santo, Health of Sciences Center, Marechal Campos av., 1468, Maruípe, 29.040-090, Vitória, ES, Brazil

    Izabela Sinara Silva Alves, Pedro Henrique Piras Coser, Willian Grassi Bautz & Marcos da Silva Pacheco

  2. Department of Coloproctology, Vitória ApartHospital, BR-101 North, km 2.38, Boa Vista II, Serra, ES, Brazil

    Giovanni José Zucoloto Loureiro & Luciano Pinto Nogueira da Gama

  3. PAT Laboratory Medicine, Constante Sodré street, no. 346, Santa Lúcia, Vitória, ES, CEP: 29.055-420, Brazil

    Flavya da Silva Souza Ribeiro

  4. Faculty of Medicine, University of São Paulo, São Paulo, Brazil

    Willian Grassi Bautz

  5. Department of Morphology, Federal University of Espírito Santo, Health of Sciences Center, Postgraduate Program in Dental Clinic (PPGCO), Marechal Campos av., 1468, Maruípe, 29.040-090, Vitória, ES, Brazil

    Karla Loureiro Almeida Coburn & Letícia Nogueira da Gama de Souza

Authors
  1. Izabela Sinara Silva Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedro Henrique Piras Coser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni José Zucoloto Loureiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luciano Pinto Nogueira da Gama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Flavya da Silva Souza Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Willian Grassi Bautz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karla Loureiro Almeida Coburn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marcos da Silva Pacheco
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Letícia Nogueira da Gama de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Letícia Nogueira da Gama de Souza.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

Authors’ Contributions

ISSA participated in all phases of this study. PHPC performed the questionnaire applied and histological analysis to identify mast cells. GJZL and LPNG were responsible to medical procedures. FR was responsible to histopathological diagnosis. WGB, KLAC, and MSP contributed to the data analysis and interpretation. LNGS designed the study and participated in all phases. All authors contributed to the manuscript writing, revision, and final approval of this paper.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alves, I.S.S., Coser, P.H.P., Loureiro, G.J.Z. et al. Fibrosis and Mast Cells in Colorectal Lesions: Significance in Adenoma-Colorectal Cancer Sequence and Association with Diet. J Gastrointest Canc 47, 278–286 (2016). https://doi.org/10.1007/s12029-016-9829-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-016-9829-1

Keywords

Search

Navigation