E-selectin and Sialyl Lewis X Expression Is Associated With Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

Abstract

To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin—positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.

Keywords

invasive micropapillary carcinoma of the breast E-selectin Sialyl Lewis X microvessel density lymph node metastasis

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References

Siriaunkgul S. , Tavassoli FA Invasive micropapillary carcinoma of the breast . Mod Pathol. 1993;6:660-662.

Luna More S. , Gonzalez B. , Acedo C. , Rodrigo I. , Luna C. Invasive micropapillary carcinoma of the breast. A new special type of invasive mammary carcinoma . Pathol Res Pract. 1994;190:668-674.

Tavassoli FA, Devillee P (eds). Pathology and Genetics of Tumours of the Breast and Female Genital Organs. World Health Organization Classification of Tumors. Lyon, France: IARC Press; 2003:35-36.

Pettinato G. , Manivel GJ , Panico L. , Sparano L. , Petrella G. Invasive micropapillary carcinoma of the breast: clinicopathologic study of 62 cases of a poorly recognized variant with highly aggressive behavior. Am J Clin Pathol. 2004 ;121:857-866.

Fu L. , Matsuyama I. , Fu XY , Liu T. , Tsuchiya S. Relationship between biologic behavior and morphologic features of invasive micropapillary carcinoma of the breast. Chin J Pathol. 2004;33:21-25.

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.

Guo XJ , Chen L. , Lang R. , Fan Y. , Zhang X. , Fu L. Invasive micropapillary carcinoma of the breast: association of pathologic features with lymph node metastasis. Am J Clin Pathol. 2006;126:740-746.

Fan Y. , Lang RG , Wang Y. , Sun BC , Fu L. Relationship between expression of cell adhesion molecules and the metastatic potential in invasive micropapillary carcinoma of breast. Chin J Pathol. 2004;33:308-311.

Vestweber D. , Blanks JE Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev. 1999; 79:181-213.

10.

Witz IP The involvement of selectins and their ligands in tumor-progression. Immunol Lett. 2006;104:89-93.

11.

Magnani JL The discovery, biology, and drug development of sialyl Lea and sialyl Lex . Arch Biochem Biophys. 2004;426:122-131.

12.

Kannagi R. , Izawa M. , Koike T. , Miyazaki K. , Kimura N. Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis . Cancer Sci. 2004;95:377-384.

13.

Renkonen J. , Paavonen T. , Renkonen R. Endothelial and epithelial expression of sialyl Lewis(x) and sialyl Lewis(a) in lesions of breast carcinoma. Int J Cancer. 1997;74: 296-300.

14.

Tei K. , Kawakami-Kimura N. , Taguchi O. , et al. Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats. Cancer Res. 2002;62:6289-6296.

15.

Carmeliet P. , Jain RK Angiogenesis in cancer and other diseases . Nature. 2000;407:249-257.

16.

Weidner N. , Semple JP , Welch WR , Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma . N Engl J Med. 1991;324:1-8.

17.

Elston CW , Ellis IO Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403-410.

18.

Greene FL , Page DL , Fleming ID , et al (eds). American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer-Verlag; 2002 :223-238.

19.

Ruco LP , Pomponi D. , Pigott R. , et al. Cytokine production (IL-1alpha, IL-1beta, and TNF alpha) and endothelial cell activation (ELAM-1 and HLA-DR) in reactive lymphadenitis, Hodgkin’s disease, and in non-Hodgkin’s lymphomas. An immunocytochemical study. Am J Pathol. 1990;137:1163-1171.

20.

Baldus SE , Mönig SP , Hanisch FG , et al. Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma . Histopathology. 2002;40:440-449.

21.

Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169-173.

22.

Fox SB , Turner GD , Gatter KC , Harris AL The increased expression of adhesion molecules ICAM-3, E- and P-selectins on breast cancer endothelium. J Pathol. 1995 ;177:369-376.

23.

Alpaugh ML , Tomlinson JS , Ye Y. , Barsky SH Relationship of Sialyl-Lewis(x/a) underexpression and E-cadherin over-expression in the lymphovascular embolus of inflammatory breast carcinoma. Am J Pathol. 2002;161:619-628.

24.

Alpaugh ML , Tomlinson JS , Kasraeian S. , Barsky SH Cooperative role of E-cadherin and sialyl-Lewis X/A-deficient MUC1 in the passive dissemination of tumor emboli in inflammatory breast carcinoma. Oncogene. 2002;21:3631-3643.

25.

Nassar H. , Pansare V. , Zhang H. , et al. Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein. Mod Pathol. 2004;17:1045-1050.

26.

Li YS , Kaneko M. , Sakamoto DG , Takeshima Y. , Inai K. The reversed apical pattern of MUC1 expression is characteristics of invasive micropapillary carcinoma of the breast. Breast Cancer. 2006;13:58-63.

27.

Hanski C. , Drechsler K. , Hanisch F. , et al. Altered glycosylation of the MUC-1 protein core contributes to the colon carcinoma-associated increase of mucin-bound sialyl-Lewis(x) expression. Cancer Res. 1993;53:4082-4088.

28.

Hanski C. , Hanski ML , Zimmer T. , Ogorek D. , Devine P. , Riecken EO Characterization of the major sialyl-Lex-positive mucins present in colon, colon carcinoma, and sera of patients with colorectal cancer. Cancer Res. 1995;55:928-933.