Detection of Cancer Stem Cells in Colorectal Cancer: Histopathological and Immunohistochemical Study

Authors

  • Nour El Hoda S. Ismaiel Pathology Department, Faculty of Medicine, Cairo University, Cairo
  • Walid M. Sharaf Pathology Department, National Research Centre, Dokki, Cairo
  • Dina O. Helmy Pathology Department, Faculty of Medicine, Cairo University, Cairo
  • Mona M. Zaki Pathology Department, National Research Centre, Dokki, Cairo
  • Manal Abd El-Magied Badawi Pathology Department, National Research Centre, Dokki, Cairo
  • Ahmed S. A. Soliman Pathology Department, National Research Centre, Dokki, Cairo

DOI:

https://doi.org/10.3889/oamjms.2016.126

Keywords:

Cancer stem cells, CD44, Colorectal carcinoma, Metastasis

Abstract

BACKGROUND: Growing evidence supports the notion that the onset of tumorigenesis could occur through cancer stem cells (CSCs). These tumour cells show low proliferative rates, high self-renewal capacity, propensity to differentiate into active proliferating tumour cells & resistance to chemoradiotherapy thus, possibly causing local recurrences & metastasis formation. CD44 has been used as a marker to isolate CSCs from colorectal carcinoma (CRC).

AIM: To investigate the immunohistochemical expression of cancer stem cells marker (CD44) in CRC and correlate its expression with the clinicopathological aspects, TNM staging and modified Dukes’ classification.

MATERIALS AND METHODS: Tumour biopsies from colectomy specimens of 60 patients with CRC were stained with hematoxylin-eosin for histological evaluation then immunostained with monoclonal antibodies against CD44 which was detected in term of negative or positive expression.

RESULTS: CD44 was demonstrated in 58.3% (35/60) of cases and showed statistically significant correlation with tumour site and histological type (p-value < 0.05). However, CD44 showed statistically insignificant inverse correlation with tumour invasiveness (T), lymph node status (N), grade, TNM stage grouping and modified Dukes’ classification, while it was directly correlated with distant metastasis (M) (p-value > 0.05). Chi-square /Fisher exact test proportion independence and the p-value are set significant at 0.05 level.

CONCLUSION: the CD44 rate of expression is higher in the colon than rectum and in adenocarcinoma than mucinous and undifferentiated carcinoma. CD44 showed statistically insignificant relation with T, N, M, grade, TNM stage grouping and modified Dukes’ classification.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

Author Biography

Manal Abd El-Magied Badawi, Pathology Department, National Research Centre, Dokki, Cairo

Pathology Department

References

Ferlay J, Shin HR, Bray F et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893–2917. https://doi.org/10.1002/ijc.25516 PMid:21351269 DOI: https://doi.org/10.1002/ijc.25516

Chun-Yan Li, Bao-Xiu Li, Yi Liang, Rui-Qing Peng, Ya Ding, Da-Zhi Xu, Xin Zhang, Zhi-Zhong Pan, De-Sen Wan, Yi-Xin Zeng, Xiao-Feng Zhu & Xiao-Shi Zhang. A Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB: Journal of Translational Medicine. 2009; 7:56. https://doi.org/10.1186/1479-5876-7-56 PMid:19583834 PMCid:PMC2715381 DOI: https://doi.org/10.1186/1479-5876-7-56

Boman BM, Wicha MS. Cancer Stem Cells: A Step toward the Cure. American Society of Clinical Oncology. 2008; 26(17):2795-2799. https://doi.org/10.1200/JCO.2008.17.7436 PMid:18539956 DOI: https://doi.org/10.1200/JCO.2008.17.7436

Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumor-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov. 2009; 8: 806– 823. https://doi.org/10.1038/nrd2137 PMid:19794444 DOI: https://doi.org/10.1038/nrd2137

Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, Carafa V, Spagnoli G, Terracciano L & Zlobec I. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer. 2010;103: 382-390. https://doi.org/10.1038/sj.bjc.6605762 PMid:20606680 PMCid:PMC2920016 DOI: https://doi.org/10.1038/sj.bjc.6605762

Hamilton SR, Bosman FT & Boffetta P. Carcinoma of the colon and rectum. In: WHO Classification of Tumors of the Digestive System. Bosman FT, Carneiro F, Hruban RH and Theise ND, (eds). 4th edition. IARC Press, Lyon, 2010:132-146.

Dukes CE, Bussey HJR & Lamb GW. The examination and classification of operation specimens of intestinal cancer. Bull INT Assoc Med Mus. 1947; 27:55-65.

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL & Trotti A. AJCC Cancer Staging Handbook, 7th edition. New York: Springer, 2010: 173-206.

Carr NJ, Emory TS & Sobin LH. Epithelial neoplasms of the appendix and colorectum. An analysis of cell proliferation, apoptosis, and expression of p53, CD44, and bcl-2. Arch Pathol Lab Med. 2002; 126:837-41. PMid:12088454 DOI: https://doi.org/10.5858/2002-126-0837-ENOTAA

Stoll M, Dalchau R & Schmidt RE. N6 Cluster report: CD44. In: Knapp W, Dörken B, Gilks WR, Rieber EP, Schmidt RE, Stein H, et al., editors. Leukocyte typing IV. White cell differentiation antigens. Proceedings of the 4th International Workshop and Conference; 1989 Feb 21-25; Vienna, Austria. Oxford, New York, Tokyo: Oxford University Press, 1989: 619-22.

Dieter SM, Ball CR, Hoffmann CM, Nowrouzi A, Herbst F, Zavidij O, Abel U, Arens A, Weichert W & Brand K et al. Distinct types of tumor-initiating cells from human colon cancer tumors and metastases. Cell Stem Cell. 2011; 9: 357–365. https://doi.org/10.1016/j.stem.2011.08.010 PMid:21982235 DOI: https://doi.org/10.1016/j.stem.2011.08.010

Huh JW, Kim HR, Kim YJ, Lee JH, Park YS, Cho SH, Joo JK. Expression of standard CD44 in human colorectal carcinoma: association with prognosis. Pathol Int. 2009; 59: 241-246. https://doi.org/10.1111/j.1440-1827.2009.02357.x PMid:19351367 DOI: https://doi.org/10.1111/j.1440-1827.2009.02357.x

Kunimura T, Yoshida T, Sugiyama T & Morohoshi T. The relationships between loss of standard CD44 expression and lymph node, liver metastasis in T3 colorectal carcinoma. J Gastrointest Canc. 2009; 40:115–118. https://doi.org/10.1007/s12029-009-9100-0 PMid:19937401 DOI: https://doi.org/10.1007/s12029-009-9100-0

Pitule P, Cedikova M, Daum O, Vojtisek J, Vycital O, Hosek P, Treska V, Hes O, Kralickova M, & Liska V. Immunohistochemical Detection of Cancer Stem Cell Related Markers CD44 and CD133 in Metastatic Colorectal Cancer Patients. BioMed Research International. 2014; 2014, Article ID 432139. DOI: https://doi.org/10.1155/2014/432139

Chen L, Jiang B, Wang Z, Liu M, Yang H, Xing J, Zhang C, Yao Z, Zhang N, Cui M & Su X. Combined preoperative CEA and CD44v6 improves prognostic value in patients with stage I and stage II colorectal cancer. Clin Transl Oncol. 2014; 16(3): 285-292. https://doi.org/10.1007/s12094-013-1069-2 PMid:23860725 DOI: https://doi.org/10.1007/s12094-013-1069-2

Khoursheed M, Mathew TC, Makar PR, Sonia L, Abul H, Asfar S, AL-Sayer H, Dashti HM & AL-Bader A. Expression of CD44s in Human Colorectal Cancer. Pathology Oncology Research. 2002; 8(3): 170–174. https://doi.org/10.1007/BF03032390 PMid:12515996 DOI: https://doi.org/10.1007/BF03032390

AL-Magrabi J, G0maa W, Bumieda A, AL-Qahtani M & AL-Ahwal M. Decreased Immunoexpression of Standard Form of CD44 Is an Independent Favourable Predictor of Nodal Metastasis in Colorectal Carcinoma. Anticancer Research. 2012; 32: 3455-3462. PMid:22843930

Peng J, Cai S, Lu H, Cai G, Lian P, Guan Z, Wang M & Xu Y. Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers. World J Gastroenterol. 2007; 13(21): 3009-3015. https://doi.org/10.3748/wjg.v13.i21.3009 PMid:17589956 PMCid:PMC4171158 DOI: https://doi.org/10.3748/wjg.v13.i21.3009

Liu D, Sun J, Zhu J, Zhou H, Zhang X & Zhang Y. Expression and clinical significance of colorectal cancer stem cell marker EpCAMhigh/CD44+ in colorectal cancer. Oncology Letters. 2014; 7: 1544-1548. https://doi.org/10.3892/ol.2014.1907 DOI: https://doi.org/10.3892/ol.2014.1907

Galizia G, Gemei M, Del Vecchio L, Zamboli A, Di Noto R, Mirabelli P, Salvatore F, Castellano P, Orditura M, De Vita F, Pinto M, Pignatelli C & Lieto E. Combined CD133/CD44 Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer. Arch Surg. 2012; 147(1):18-24. https://doi.org/10.1001/archsurg.2011.795 PMid:22250106 DOI: https://doi.org/10.1001/archsurg.2011.795

Gunthert U. CD44 in malignant disorders. Curr Top Microbiol Immunol. 1996; 213(1): 271–285. https://doi.org/10.1007/978-3-642-61107-0_16 PMid:8814992 DOI: https://doi.org/10.1007/978-3-642-61107-0_16

Published

2016-12-07

How to Cite

1.
Ismaiel NEHS, Sharaf WM, Helmy DO, Zaki MM, Badawi MAE-M, Soliman ASA. Detection of Cancer Stem Cells in Colorectal Cancer: Histopathological and Immunohistochemical Study. Open Access Maced J Med Sci [Internet]. 2016 Dec. 7 [cited 2024 Apr. 24];4(4):543-7. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2016.126

Issue

Section

A - Basic Science