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Open Access 01-12-2012 | Original Paper

Immunohistochemical detection of CD133 is associated with tumor regression grade after chemoradiotherapy in rectal cancer

Authors: Kumiko Hongo, Shinsuke Kazama, Eiji Sunami, Nelson H. Tsuno, Koki Takahashi, Hirokazu Nagawa, Joji Kitayama

Published in: Medical Oncology | Issue 4/2012

Abstract

CD133 has been identified as a putative cancer stem cell (CSC) marker in various cancers including colorectal cancer. The relation between CD133 expression and biological characteristics of colorectal cancer remains to be clarified. Protein expression of CD133 was immunohistochemically evaluated in surgical specimens of 225 patients with colorectal cancer who were treated by surgery, as well as those of 78 patients with rectal cancer who received preoperative chemoradiotherapy (CRT) followed by curative resection. The correlation between CD133 expression and clinicopathological features, tumor recurrence and overall survival was analyzed in both populations. Among 225 colorectal cancers without CRT, 93 (41.3%) were positive for CD133 expression, which was enhanced in cases with advanced T stage and venous invasion. Moreover, CD133 was positive in 47 (60.3%) of 78 cases with CRT, which was significantly higher than the CD133-positive rate in non-CRT specimens (P = 0.05). Expression of CD133 was independently correlated with the histological tumor regression grade (P < 0.01). These results suggest that CD133 is not a distinctive colorectal CSC marker; expression of CD133 is suggested to be one of the key factors associated with resistance to CRT in colorectal cancer.

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11. doi:10.1038/35102167.PubMedCrossRef

Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8. doi:10.1038/367645a0.PubMedCrossRef

Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121(6):823–35. doi:10.1016/j.cell.2005.03.032.PubMedCrossRef

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100(7):3983–8. doi:10.1073/pnas.0530291100.PubMedCrossRef

Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA. 2004;101(3):781–6. doi:10.1073/pnas.0307618100.PubMedCrossRef

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401. doi:10.1038/nature03128.PubMedCrossRef

Wang S, Garcia AJ, Wu M, Lawson DA, Witte ON, Wu H. Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci USA. 2006;103(5):1480–5. doi:10.1073/pnas.0510652103.PubMedCrossRef

Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005;37(4):715–9. doi:10.1016/j.biocel.2004.08.010.PubMedCrossRef

O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–10. doi:10.1038/nature05372.PubMedCrossRef

10.

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–5. doi:10.1038/nature05384.PubMedCrossRef

11.

Ieta K, Tanaka F, Haraguchi N, Kita Y, Sakashita H, Mimori K, et al. Biological and genetic characteristics of tumor-initiating cells in colon cancer. Ann Surg Oncol. 2008;15(2):638–48. doi:10.1245/s10434-007-9605-3.PubMedCrossRef

12.

Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63(18):5821–8.PubMed

13.

Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65(23):10946–51. doi:10.1158/0008-5472.CAN-05-2018.PubMedCrossRef

14.

Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007;132(7):2542–56. doi:10.1053/j.gastro.2007.04.025.PubMedCrossRef

15.

Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133− metastatic colon cancer cells initiate tumors. J Clin Invest. 2008;118(6):2111–20. doi:10.1172/JCI34401.PubMed

16.

Du L, Wang H, He L, Zhang J, Ni B, Wang X, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res. 2008;14(21):6751–60. doi:10.1158/1078-0432.CCR-08-1034.PubMedCrossRef

17.

Dittfeld C, Dietrich A, Peickert S, Hering S, Baumann M, Grade M, et al. CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell lines HCT-116. Radiother Oncol. 2009;92(3):353–61. doi:10.1016/j.radonc.2009.06.034.PubMedCrossRef

18.

Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nature Rev Cancer. 2005;5(4):275–84. doi:10.1038/nrc1590.CrossRef

19.

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60. doi:10.1038/nature05236.PubMedCrossRef

20.

Lomonaco SL, Finniss S, Xiang C, Decarvalho A, Umansky F, Kalkanis SN, et al. The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells. Int J Cancer. 2009;125(3):717–22. doi:10.1002/ijc.24402.PubMedCrossRef

21.

Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16(12):3488–98. doi:10.1245/s10434-009-0617-z.PubMedCrossRef

22.

Yasuda H, Tanaka K, Saigusa S, Toiyama Y, Koike Y, Okugawa Y, et al. Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer. Oncol Rep. 2009;22(4):709–17.PubMed

23.

Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1(4):389–402. doi:10.1016/j.stem.2007.08.001.PubMedCrossRef

24.

Hongo K, Tanaka J, Tsuno NH, Kawai K, Nishikawa T, Shuno Y, et al. CD133(−) cells, derived from a single human colon cancer cell line, are more resistant to 5-fluorouracil (FU) than CD133(+) cells, dependent on the beta1-integrin signaling. J Surg Res. 2011. doi:10.1016/j.jss.2011.03.076.PubMed

25.

TNM Classification of Malignant Tumours, 7th ed (2009).

26.

International Classification of Diseases for Oncology (2000).

27.

General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum, and Anus (2006).

28.

Maeda S, Shinchi H, Kurahara H, Mataki Y, Maemura K, Sato M, et al. CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer. Br J Cancer. 2008;98(8):1389–97. doi:10.1038/sj.bjc.6604307.PubMedCrossRef

29.

Li CY, Li BX, Liang Y, Peng RQ, Ding Y, Xu DZ, et al. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB. J Transl Med. 2009;7:56. doi:10.1186/1479-5876-7-56.PubMedCrossRef

30.

Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, et al. 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(3):382–90. doi:10.1038/sj.bjc.6605762.PubMedCrossRef

31.

Viera AJ, Garrett JM. Understanding interobserver agreement: the kappa statistic. Fam Med. 2005;37(5):360–3.PubMed

32.

Horst D, Kriegl L, Engel J, Kirchner T, Jung A. CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer. 2008;99(8):1285–9. doi:10.1038/sj.bjc.6604664.PubMedCrossRef

33.

Kojima M, Ishii G, Atsumi N, Fujii S, Saito N, Ochiai A. Immunohistochemical detection of CD133 expression in colorectal cancer: a clinicopathological study. Cancer Sci. 2008;99(8):1578–83. doi:10.1111/j.1349-7006.2008.00849.x.PubMedCrossRef

34.

Horst D, Kriegl L, Engel J, Jung A, Kirchner T. CD133 and nuclear beta-catenin: the marker combination to detect high risk cases of low stage colorectal cancer. Eur J Cancer. 2009;45(11):2034–40. doi:10.1016/j.ejca.2009.04.004.PubMedCrossRef

35.

Ong CW, Kim LG, Kong HH, Low LY, Iacopetta B, Soong R, et al. CD133 expression predicts for non-response to chemotherapy in colorectal cancer. Mod Pathol. 2010;23(3):450–7. doi:10.1038/modpathol.2009.181.PubMedCrossRef

36.

37.

Choi D, Lee HW, Hur KY, Kim JJ, Park GS, Jang SH, et al. Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol. 2009;15(18):2258–64.PubMedCrossRef

38.

Wang Q, Chen ZG, Du CZ, Wang HW, Yan L, Gu J. Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer. Histopathology. 2009;55(3):284–93. doi:10.1111/j.1365-2559.2009.03378.x.PubMedCrossRef

39.

Li G, Liu C, Yuan J, Xiao X, Tang N, Hao J, et al. CD133(+) single cell-derived progenies of colorectal cancer cell line SW480 with different invasive and metastatic potential. Clin Exp Metastasis. 2010;27(7):517–27. doi:10.1007/s10585-010-9341-0.PubMedCrossRef

40.

Kojima M, Ishii G, Atsumi N, Nishizawa Y, Saito N, Ochiai A. CD133 expression in rectal cancer after preoperative chemoradiotherapy. Cancer Sci. 2010;101(4):906–12. doi:10.1111/j.1349-7006.2009.01478.x.PubMedCrossRef

41.

Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Kawamoto A, et al. Immunohistochemical features of CD133 expression: association with resistance to chemoradiotherapy in rectal cancer. Oncol Rep. 2010;24(2):345–50.PubMedCrossRef

42.

43.

Haylock DN, Nilsson SK. Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle. 2005;4(10):1353–5.PubMedCrossRef

44.

De Filippis L, Delia D. Hypoxia in the regulation of neural stem cells. Cell Mol Life Sci. 2011. doi:10.1007/s00018-011-0723-5.

45.

Bar EE, Lin A, Mahairaki V, Matsui W, Eberhart CG. Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres. Am J Pathol. 2010;177(3):1491–502. doi:10.2353/ajpath.2010.091021.PubMedCrossRef

46.

Guedj N, Bretagnol F, Rautou PE, Deschamps L, Cazals-Hatem D, Bedossa P, et al. Predictors of tumor response after preoperative chemoradiotherapy for rectal adenocarcinomas. Hum Pathol. 2011. doi:10.1016/j.humpath.2011.01.015.PubMed

47.

Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11(6):393–410. doi:10.1038/nrc3064.PubMedCrossRef

48.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106–30. doi:56/2/106.PubMedCrossRef

49.

Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453–8. doi:10.1038/nrc1098.PubMedCrossRef

Title: Immunohistochemical detection of CD133 is associated with tumor regression grade after chemoradiotherapy in rectal cancer
Authors: Kumiko Hongo
Shinsuke Kazama
Eiji Sunami
Nelson H. Tsuno
Koki Takahashi
Hirokazu Nagawa
Joji Kitayama
Publication date: 01-12-2012
Publisher: Springer US
Published in: Medical Oncology / Issue 4/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-012-0161-8

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