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Immunohistochemical analyses of CD44 variant isoforms in invasive micropapillary carcinoma of the breast: comparison with a concurrent conventional invasive carcinoma of no special type component

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Abstract

Background

Invasive micropapillary carcinoma (IMPC) is a distinct histopathological variant of breast carcinoma and frequently develops lymph node metastases. CD44 is a family of transmembrane glycoprotein receptors with multiple variant isoforms (CD44v), which have tissue-specific expression. Previous studies have demonstrated a loss or gain of CD44v and CD44 standard form (CD44s) expression in breast carcinomas. In this study, we analyzed the immunoprofiles of CD44s, CD44v6, and CD44v9 in IMPC and compared them with those in a concurrent invasive carcinoma of no special type (ICNST) component, thus clarifying the significance of CD44 expression in IMPC.

Methods

Twenty-one consecutive cases of mixed IMPC were included in this study. The expression statuses of CD44s, CD44v6, and CD44v9 in both the IMPC and ICNST components were analyzed semiquantitatively by immunohistochemistry.

Results

The immunohistochemical scores of CD44s, CD44v6, and CD44v9 were significantly decreased in the IMPC component compared to the ICNST component (p = 0.00335 for CD44s, p = 0.000982 for CD44v6, and p = 0.00271 for CD44v9). Moreover, the immunohistochemical scores of CD44v6 in the IMPC component and CD44v9 in the ICNST component of lymph node metastasis cases were significantly lower compared to cases without lymph node metastasis (p < 0.01).

Conclusions

Decreased CD44 expression may play an important role in promoting lymph node metastasis in IMPC through an inability or decreased capacity to bind with the surrounding stroma. Moreover, high CD44s+ expression levels in the concurrent ICNST component may be related to the development of IMPC.

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References

  1. Reis-Filho JS, Ellis IO. Invasive micropapillary carcinoma. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, editors. WHO classification of tumours of the breast. Lyon: International Agency for Research on Cancer; 2012. p. 65–6.

    Google Scholar 

  2. Nassar H, Wallis T, Andea A, Dey J, Adsay V, Visscher D. Clinicopathologic analysis of invasive micropapillary differentiation in breast carcinoma. Mod Pathol. 2001;14:836–41.

    Article  CAS  PubMed  Google Scholar 

  3. Zekioglu O, Erhan Y, Ciris M, Bayramoglu H, Özdemir N. Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma. Histopathology. 2004;44:18–23.

    Article  CAS  PubMed  Google Scholar 

  4. Kuroda H, Sakamoto G, Ohnisi K, Itoyama S. Clinical and pathologic features of invasive micropapillary carcinoma. Breast Cancer. 2004;11:169–74.

    Article  PubMed  Google Scholar 

  5. Jackson DG, Buckley J, Bell JI. Multiple variants of the human lymphocytes homing receptor CD44 generated by insertions at a single site in the extracellular domain. J Biol Chem. 1992;267:4732–9.

    CAS  PubMed  Google Scholar 

  6. Sneath RJ, Mangham DC. The normal structure and function of CD44 and its role in neoplasia. Mod Pathol. 1998;51:191–200.

    CAS  Google Scholar 

  7. Grass GD, Tolliver LB, Bratoeva M, Toole BP. CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness. J Biol Chem. 2013;288:26089–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hirata K, Suzuki H, Imaeda H, Matsuzaki J, Tsugawa H, Nagano O, et al. CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence. Br J Cancer. 2013;109:379–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Avoranta ST, Korkeila EA, Syrjänen KJ, Pyrhönen SO, Sundström JT. Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence. World J Gastroenterol. 2012;18:4549–56.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liu YJ, Yan PS, Li J, Jia JF. Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer. World J Gastroenterol. 2005;11:6601–6.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhao S, He JL, Qiu ZX, Chen NY, Luo Z, Chen BJ, et al. Prognostic value of CD44 variant exon 6 expression in non-small cell lung cancer: a meta-analysis. Asia Pac J Cancer Prev. 2014;15:6761–6.

    Article  Google Scholar 

  12. Franzmann EJ, Weed DT, Civantos FJ, Goodwin WJ, Bourguignon LY. A novel CD44 v3 isoform is involved in head and neck squamous cell carcinoma progression. Otolaryngol Head Neck Surg. 2001;124:426–32.

    Article  CAS  PubMed  Google Scholar 

  13. Gotoda T, Matsumura Y, Kondo H, Ono H, Kanamoto A, Kato H, et al. Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma. Gut. 2000;46:14–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hong SC, Song JY, Lee JK, Lee NW, Kim SH, Yeom BW, et al. Significance of CD44v6 expression in gynecologic malignancies. J Obstet Gynaecol Res. 2006;32:379–86.

    Article  CAS  PubMed  Google Scholar 

  15. Bankfalvi A, Terpe HJ, Breukelmann D, Bier B, Rempe D, Pschadka G, et al. Gains and losses of CD44 expression during breast carcinogenesis and tumour pregression. Histopathology. 1998;33:107–16.

    Article  CAS  PubMed  Google Scholar 

  16. Afify A, Purnell P, Nguyen L. Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and invasion. Exp Mol Pathol. 2009;86:95–100.

    Article  CAS  PubMed  Google Scholar 

  17. Li W, Liu F, Lei T, Xu X, Liu B, Cui L, et al. The clinicopathological significance of CD44+/CD24−/low and CD24+ tumor cells in invasive micropapillary carcinoma of the breast. Pathol Res Pract. 2010;206:828–34.

    Article  CAS  PubMed  Google Scholar 

  18. Simonetti S, Terracciano L, Zlobec I, Kilic E, Stasio L, Quarto M, et al. Immunophenotyping analysis in invasive micropapillary carcinoma of the breast: role of CD24 and CD44 isoforms expression. Breast. 2012;21:165–70.

    Article  PubMed  Google Scholar 

  19. Gong Y, Sun X, Huo L, Wiley EL, Rao MS. Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast. Histopathology. 2005;46:24–30.

    Article  CAS  PubMed  Google Scholar 

  20. Misra S, Heldin P, Hascall VC, Karamanos NK, Skandalis SS, Markwald RR, et al. HA–CD44 interactions as potential targets for cancer therapy. FEBS J. 2011;278:1429–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zöller M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 2011;11:254–67.

    Article  PubMed  Google Scholar 

  22. Olsson E, Honeth G, Bendahl P, Saal L, Gruvberger-Saal S, Ringner M, et al. CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer. 2011;11:418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chuthapisith S, Eremin J, El-Sheemey M, Eremin O. Breast cancer chemoresistance: emerging importance of cancer stem cells. Surg Oncol. 2010;19:27–32.

    Article  PubMed  Google Scholar 

  24. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, et al. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 2006;8:R59.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Phillips TM, McBride WH, Pajonk F. The response of CD24 (−/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst. 2006;98:1777–85.

    Article  PubMed  Google Scholar 

  26. Brown RL, Reinke LM, Damerow MS, Perez D, Chodosh LA, Yang J, et al. CD44 splice isoform switching in human and mouse epithelium is essential for epithelial–mesenchymal transition and breast cancer progression. J Clin Invest. 2011;121:1064–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Mitsuaki Ishida.

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The authors declare no conflict of interest.

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T. Umeda and M. Ishida contributed equally to this work.

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Umeda, T., Ishida, M., Murata, S. et al. Immunohistochemical analyses of CD44 variant isoforms in invasive micropapillary carcinoma of the breast: comparison with a concurrent conventional invasive carcinoma of no special type component. Breast Cancer 23, 869–875 (2016). https://doi.org/10.1007/s12282-015-0653-4

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  • DOI: https://doi.org/10.1007/s12282-015-0653-4

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