Journal of Cancer Research and Clinical Oncology

, Volume 140, Issue 8, pp 1271–1281 | Cite as

Aberrant expression of CD227 is correlated with tumor characteristics and invasiveness of breast carcinoma

  • Ya-Wen Wang
  • Duan-Bo Shi
  • Ya-Min Liu
  • Yan-Lin Sun
  • Xu Chen
  • Shuai Xiang
  • Qiang Fu
  • Jun-Min Wei
  • Peng Gao
Original Article – Cancer Research



Increasing evidences demonstrate that CD227 plays a crucial role in the development and progression of breast cancer. However, the function of CD227 in breast carcinoma was still controversial and the investigation on CD227 in Asian race was scarce.


To investigate the relationship between CD227 and tumor characteristics of breast carcinoma, CD227, estrogen receptor (ER), progesterone receptor (PR), Her2⁄neu and Ki-67 were detected by immunohistochemistry in a series of 227 patients. The Kaplan–Meier method and log-rank tests were used to estimate the correlation between CD227 expression and patients’ prognosis. Furthermore, in vitro invasion assay was performed to examine the effect of CD227 on the invasiveness of breast carcinoma cells after transfection with CD227 cDNA or antisense phosphorothioate oligodeoxynucleotides (ASODN) against CD227 mRNA.


Our data demonstrate that the cytoplasm staining and high expression of CD227 were positively related to the aggressiveness of breast cancer. Both circumferential membrane staining and cytoplasm staining were associated with lymph node metastasis. Moreover, the cytoplasm staining and overexpression of CD227 were found to be related to Her-2/neu positivity, higher Ki-67 positivity and poorer survival of patients. We further demonstrated that the invasion ability of breast carcinoma cells could be enhanced or inhibited by CD227 cDNA or ASODN, respectively.


We conclude that the aberrant expression of CD227, especially cytoplasm staining could be predictive for tumor aggressiveness, lymph node metastasis, poorer outcome of patients with breast cancers. And CD227 could promote the invasion ability of breast cancer cells, suggesting a potential role of CD227 as an oncogene in breast carcinoma.


Breast carcinoma CD227 Tumor characteristics Invasiveness Antisense phosphorothioate oligodeoxynucleotides Prognosis 

Supplementary material

432_2014_1676_MOESM1_ESM.tif (3.1 mb)
Supplementary material 1 (TIFF 3173 kb)
432_2014_1676_MOESM2_ESM.doc (30 kb)
Supplementary material 2 (DOC 29 kb)


  1. Acs G, Esposito NN, Rakosy Z, Laronga C, Zhang PJ (2010) Invasive ductal carcinomas of the breast showing partial reversed cell polarity are associated with lymphatic tumor spread and may represent part of a spectrum of invasive micropapillary carcinoma. Am J Surg Pathol 34(11):1637–1646. doi:10.1097/PAS.0b013e3181f5539c PubMedGoogle Scholar
  2. Agrawal B, Krantz MJ, Parker J, Longenecker BM (1998) Expression of MUC1 mucin on activated human T cells: implications for a role of MUC1 in normal immune regulation. Cancer Res 58(18):4079–4081PubMedGoogle Scholar
  3. Angus B, Napier J, Purvis J, Ellis IO, Hawkins RA, Carpenter F, Horne CH (1986) Survival in breast cancer related to tumour oestrogen receptor status and immunohistochemical staining for NCRC 11. J Pathol 149(4):301–306. doi:10.1002/path.1711490406 PubMedCrossRefGoogle Scholar
  4. Arnerlov C, Ellis IO, Emdin SO (1988) Monoclonal antibody NCRC 11 reactivity with advanced breast carcinoma: lack of prognostic value. Histopathology 13(6):695–697PubMedCrossRefGoogle Scholar
  5. Birner P, Oberhuber G, Stani J, Reithofer C, Samonigg H, Hausmaninger H, Kubista E, Kwasny W, Kandioler-Eckersberger D, Gnant M, Jakesz R, Austrian B, Colorectal Cancer Study G (2001) Evaluation of the United States Food and drug administration-approved scoring and test system of HER-2 protein expression in breast cancer. Clin Cancer Res 7(6):1669–1675PubMedGoogle Scholar
  6. Borg A, Tandon AK, Sigurdsson H, Clark GM, Ferno M, Fuqua SA, Killander D, McGuire WL (1990) HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res 50(14):4332–4337PubMedGoogle Scholar
  7. Brugger W, Buhring HJ, Grunebach F, Vogel W, Kaul S, Muller R, Brummendorf TH, Ziegler BL, Rappold I, Brossart P, Scheding S, Kanz L (1999) Expression of MUC-1 epitopes on normal bone marrow: implications for the detection of micrometastatic tumor cells. J Clin Oncol 17(5):1535–1544PubMedGoogle Scholar
  8. Carraway KL 3rd, Funes M, Workman HC, Sweeney C (2007) Contribution of membrane mucins to tumor progression through modulation of cellular growth signaling pathways. Curr Topics Develop Biol 78:1–22. doi:10.1016/S0070-2153(06)78001-2 CrossRefGoogle Scholar
  9. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156–159. doi:10.1006/abio.1987.9999 PubMedCrossRefGoogle Scholar
  10. Cooke T, Reeves J, Lanigan A, Stanton P (2001) HER2 as a prognostic and predictive marker for breast cancer. Ann Oncol 12(Suppl 1):S23–S28PubMedCrossRefGoogle Scholar
  11. de Roos MA, van der Vegt B, Peterse JL, Patriarca C, de Vries J, de Bock GH, Wesseling J (2007) The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome in ‘pure’ ductal carcinoma in situ of the breast. Histopathology 51(2):227–238. doi:10.1111/j.1365-2559.2007.02754.x PubMedCrossRefGoogle Scholar
  12. Dyomin VG, Palanisamy N, Lloyd KO, Dyomina K, Jhanwar SC, Houldsworth J, Chaganti RS (2000) MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets. Blood 95(8):2666–2671PubMedGoogle Scholar
  13. Fisher B, Redmond C, Fisher ER, Caplan R (1988) Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06. J Clin Oncol 6(7):1076–1087PubMedGoogle Scholar
  14. Gao P, Xing AY, Zhou GY, Zhang TG, Zhang JP, Gao C, Li H, Shi DB (2013) The molecular mechanism of microRNA-145 to suppress invasion-metastasis cascade in gastric cancer. Oncogene 32(4):491–501. doi:10.1038/onc.2012.61 PubMedCrossRefGoogle Scholar
  15. Hayes DF, Mesa-Tejada R, Papsidero LD, Croghan GA, Korzun AH, Norton L, Wood W, Strauchen JA, Grimes M, Weiss RB et al (1991) Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study. J Clin Oncol 9(7):1113–1123PubMedGoogle Scholar
  16. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. Cancer J Clinic 61(2):69–90. doi:10.3322/caac.20107 CrossRefGoogle Scholar
  17. Kohlgraf KG, Gawron AJ, Higashi M, Meza JL, Burdick MD, Kitajima S, Kelly DL, Caffrey TC, Hollingsworth MA (2003) Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line. Cancer Res 63(16):5011–5020PubMedGoogle Scholar
  18. Li YS, Kaneko M, Sakamoto DG, Takeshima Y, Inai K (2006) The reversed apical pattern of MUC1 expression is characteristics of invasive micropapillary carcinoma of the breast. Breast Cancer 13(1):58–63PubMedCrossRefGoogle Scholar
  19. McGuckin MA (2001) CD227 (MUC1)—summary and workshop report. In: Mason D (ed) Leucocyte typing VII. Oxford University, Oxford, pp 54–56Google Scholar
  20. McGuckin MA, Walsh MD, Hohn BG, Ward BG, Wright RG (1995) Prognostic significance of MUC1 epithelial mucin expression in breast cancer. Hum Pathol 26(4):432–439PubMedCrossRefGoogle Scholar
  21. Nakamori S, Ota DM, Cleary KR, Shirotani K, Irimura T (1994) MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology 106(2):353–361PubMedGoogle Scholar
  22. Nassar H, Pansare V, Zhang H, Che M, Sakr W, Ali-Fehmi R, Grignon D, Sarkar F, Cheng J, Adsay V (2004) Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein. Mod Pathol 17(9):1045–1050. doi:10.1038/modpathol.3800166 PubMedCrossRefGoogle Scholar
  23. Parham DM, Slidders W, Robertson AJ (1988) Quantitation of human milk fat globule (HMFG1) expression in breast carcinoma and its association with survival. J Clin Pathol 41(8):875–879PubMedCentralPubMedCrossRefGoogle Scholar
  24. Rahn JJ, Dabbagh L, Pasdar M, Hugh JC (2001) The importance of MUC1 cellular localization in patients with breast carcinoma: an immunohistologic study of 71 patients and review of the literature. Cancer 91(11):1973–1982PubMedCrossRefGoogle Scholar
  25. Rakha EA, Boyce RW, Abd El-Rehim D, Kurien T, Green AR, Paish EC, Robertson JF, Ellis IO (2005) Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol 18(10):1295–1304. doi:10.1038/modpathol.3800445 PubMedCrossRefGoogle Scholar
  26. Smith NL, Catrou PG, Payne G, Kellogg AE (2004) Patterns of expression of the DS6-glycoform of MUC1 correlates with known prognostic indicators in breast cancer. In: AACR Meeting Abstracts, 2004. p 239Google Scholar
  27. Suwa T, Hinoda Y, Makiguchi Y, Takahashi T, Itoh F, Adachi M, Hareyama M, Imai K (1998) Increased invasiveness of MUC1 and cDNA-transfected human gastric cancer MKN74 cells. Int J Cancer 76(3):377–382PubMedCrossRefGoogle Scholar
  28. Treon SP, Mollick JA, Urashima M, Teoh G, Chauhan D, Ogata A, Raje N, Hilgers JH, Nadler L, Belch AR, Pilarski LM, Anderson KC (1999) Muc-1 core protein is expressed on multiple myeloma cells and is induced by dexamethasone. Blood 93(4):1287–1298PubMedGoogle Scholar
  29. van der Vegt B, de Roos MA, Peterse JL, Patriarca C, Hilkens J, de Bock GH, Wesseling J (2007) The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma. Histopathology 51(3):322–335. doi:10.1111/j.1365-2559.2007.02757.x PubMedCrossRefGoogle Scholar
  30. Wreesmann VB, Sieczka EM, Socci ND, Hezel M, Belbin TJ, Childs G, Patel SG, Patel KN, Tallini G, Prystowsky M, Shaha AR, Kraus D, Shah JP, Rao PH, Ghossein R, Singh B (2004) Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker. Cancer Res 64(11):3780–3789. doi:10.1158/0008-5472.CAN-03-1460 PubMedCrossRefGoogle Scholar
  31. Wykes M, MacDonald KP, Tran M, Quin RJ, Xing PX, Gendler SJ, Hart DN, McGuckin MA (2002) MUC1 epithelial mucin (CD227) is expressed by activated dendritic cells. J Leukocyte Biol 72(4):692–701PubMedGoogle Scholar
  32. Yilmaz M, Christofori G (2010) Mechanisms of motility in metastasizing cells. Mol Cancer Res 8(5):629–642. doi:10.1158/1541-7786.MCR-10-0139 PubMedCrossRefGoogle Scholar
  33. Yonezawa S, Goto M, Yamada N, Higashi M, Nomoto M (2008) Expression profiles of MUC1, MUC2, and MUC4 mucins in human neoplasms and their relationship with biological behavior. Proteomics 8(16):3329–3341. doi:10.1002/pmic.200800040 PubMedCrossRefGoogle Scholar
  34. Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S, Kitajima S, Goto M (2011) Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int 61(12):697–716. doi:10.1111/j.1440-1827.2011.02734.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ya-Wen Wang
    • 1
  • Duan-Bo Shi
    • 1
  • Ya-Min Liu
    • 1
    • 2
  • Yan-Lin Sun
    • 1
  • Xu Chen
    • 1
  • Shuai Xiang
    • 1
  • Qiang Fu
    • 1
  • Jun-Min Wei
    • 1
    • 3
  • Peng Gao
    • 1
  1. 1.Department of Pathology, School of MedicineShandong UniversityJinanPeople’s Republic of China
  2. 2.Department of PathologyLaiwu Steel Affiliated Hospital of Taishan Medical CollegeLaiwuPeople’s Republic of China
  3. 3.Department of Chemotherapy, Qi Lu HospitalShandong UniversityJinanPeople’s Republic of China

Personalised recommendations