nach oben

Erschienen in:

22.10.2015 | Original Article

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

verfasst von: Tomoko Umeda, Mitsuaki Ishida, Satoshi Murata, Tsuyoshi Mori, Yuki Kawai, Naoko Itoi, Kaori Tomida, Akie Tanaka, Sachiko Sakai, Mina Kitamura, Yoshihiro Kubota, Ryoji Kushima, Masaji Tani

Erschienen in: Breast Cancer | Ausgabe 6/2016

Einloggen, um Zugang zu erhalten

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.

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.

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.CrossRefPubMed

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.CrossRefPubMed

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

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.PubMed

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

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

21.

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

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

Titel: 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
verfasst von: Tomoko Umeda
Mitsuaki Ishida
Satoshi Murata
Tsuyoshi Mori
Yuki Kawai
Naoko Itoi
Kaori Tomida
Akie Tanaka
Sachiko Sakai
Mina Kitamura
Yoshihiro Kubota
Ryoji Kushima
Masaji Tani
Publikationsdatum: 22.10.2015
Verlag: Springer Japan
Erschienen in: Breast Cancer / Ausgabe 6/2016
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-015-0653-4

Springer Medizin

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