Epithelial cadherins and associated molecules in invasive lobular breast cancer

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Objective: to estimate the expression of cell adhesion molecules E- and P-cadherin, as well as that of cadherin-catenin complexes in invasive lobular breast cancer (BC) cells. Material and methods. 250 cases of postoperative material from patients diagnosed with invasive lobular BC were studied. The expressions of cell adhesion molecules E-cadherin, P-cadherin, β-catenin, p120 catenin, and vimentin were determined by immunohistochemical assay in all cases. The examined cases were divided into molecular biological subtypes, based on the evaluation of estrogen receptors (ER), progesterone receptors (PR), HER-2/neu, and Ki-67 proliferative index. Results. The membrane expression of E-cadherin on the tumor cells was found to be preserved in 93%; the cytoplasmic expression of β-catenin and p120-catenin appeared in 60 and 72% of cases, respectively. The expression of P-cadherin was detected in 82% of cases. The coexpression of E- and P-cadherin was noted in 90% of all the examined cases. There was a correlation between the expression of E- and P-cadherins (V=0.34; p<0.05). Conclusion. The BC cells showed the coexpression of E- and P-cadherins, as well as release of the molecules β- and p120-catenins into the cytoplasm of tumor cells, which leads to the activation of intracellular mechanisms for changing the structure of the cytoskeleton and the level of proliferation. The above-mentioned mechanisms are accompanied by the activation of epithelial-mesenchymal transition. The intracellular mechanisms resulted in progressive cancer and its metastasis

Keywords:

E-cadherin

P-cadherin

p120-catenin

β-catenin

epithelial-mesenchymal transition

invasive lobular breast cancer

Authors:

Brilliant Yu.M.

Institute for Medical Cell Technologies, Ministry of Health of the Sverdlovsk Region, Yekaterinburg, Russia;
Ural State Medical University, Ministry of Health of Russia, Yekaterinburg, Russia

Brilliant A.A.

Institute of Medical Cell Technologies

Sazonov S.V.

GBUZ SO "Institut meditsinskikh kletochnykh tekhnologiĭ", Ekaterinburg

List of references:

Halbleib JM, Nelson JM. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20(23):3199-3214. doi:10.1101/gad.1486806
Zasadkevich Yu, Sazonov S, Brilliant A. Role of cadherins in health and in developing breast cancer. Arkhiv patologii. 2015;77(3):57-64. (In Russ.) doi:10.17116/patol201577357-64
Kotb AM, Hierholzer A, Kemler R. Replacement of E-cadherin by N-cadherin in the mammary gland leads to fibrocystic changes and tumor formation. Breast Cancer Res. 2011;13:R104. doi:10.1186/bcr3046
Weigelt B, Peterse JL, van't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005;5(8):591-602. doi:10.1038/nrc1670
Frank G, Zavalishina L, Andreeva Yu. Status of extracellular matrix and adhesion markers in urothelial cancer of the urinary bladder. Arkhiv patologii. 2005;67(3):11-14. (In Russ.)
Cowin P, Rowlands W, Hatsell SJ. Cadherins and catenins in breast cancer. Curr Opin Cell Biol. 2005;17(5):499-508. doi:10.1016/j.ceb.2005.08.014
Qureshi HS, Linden MD, Divine G, Raju UB. E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters. Am J Clin Pathol. 2006;125(3):377-385. doi:10.1309/wmx7drwtfvqp2lqt
Shi Y, Liu X, Sun Y, Wu D, Qiu A, Cheng H, Wu C, Wang X. Decreased expression and prognostic role of EHD2 in human breast carcinoma: correlation with E-cadherin. J Mol Histol. 2015;46(2):221-231. doi:10.1007/s10735-015-9614-7
Frank G, Zavalishina L, Pozharisskii K, eds. Breast cancer. A practical guide for doctors [Rak molochnoi zhelezy. Prakticheckoe rukovodstvo dlya vrachei]. Moscow: Prakticheskaya meditsina; 2014. (In Russ.)
Brilliant AA, Sazonov SV, Zasadkevich YM. Chapter 21. Modification of receptor status in groups of proliferative activity of breast carcinomas. In: Joswik R, Zaikov GE, Haghi AK, eds. Life chemistry research. Biological Systems. Apple Academic Press; 2015:247-255. doi:10.1201/b18527-25
Semiglazov V, Paltuev R. Semiglazova T, et al. Clinical recommendations at breast cancer diagnostics and treatment [Klinicheskie rekomendatsii po diagnostike i lecheniyu raka molochnoi zhelezy]. St. Petersburg: ABV-press; 2013. (In Russ.)
Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 Index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101(10):736-750. doi:10.1093/jnci/djp082
Kowalski PG, Rubin MA, Kleer CG. E-cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res. 2003;5:R217. doi:10.1186/bcr651
Vieira AF, Ricardo S, Ablett MP, Dionísio MR, Mendes N, Albergaria A, et al P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties in Basal-like breast cancer. Stem cells. 2012;30(5):854-864. doi:10.1002/stem.1075
Paredes J, Figueiredo J, Albergaria A, Oliveira P, Carvalho J, Ribeiro AS, et al. Epithelial E- and P-cadherins: role and clinical significance in cancer. Biochim Biophys Acta. 2012;1826(2):297-311. doi:10.1016/j.bbcan.2012.05.002
Ng TL, Gown AM, Barry TS, Cheang MCU, Chan AKW, Turbin DA, et al. Nuclear beta-catenin in mesenchymal tumors. Mod Pathol. 2005;18:68-74. doi:10.1038/modpathol.3800272
Ikeda S, Fujimori M, Shibata S, Okajima M, Ishizaki Y, Kurihara T, et al. Combined immunochemistry of β-catenin, cytokeratin 7, and cytokeratin 20 is useful in discriminating primary lung adenocarcinomas from metastatic colorectal cancer. BMC Cancer. 2006;6(31). doi:10.1186/1471-2407-6-31
Liu Y, Wang Y, Zhang Y, Miao Y, Zhao Y, Zhang PX, et al. Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer. Lung Cancer. 2009;63(3):375-382. doi:10.1016/j.lungcan.2008.12.012
Sarrió D, Pérez-Mies B, Hardisson D, Moreno-Bueno G, Suárez A, Cano A, et al. Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. Oncogene. 2004;23:3272-3283. doi:10.1038/sj.onc.1207439
Korsching E, Packeisen J, Liedtke C, Hungermann D, Wülfing P, van Diest PJ, et al. The origin of vimentin expression in invasive breast cancer: epithelial—mesenchymal transition, myoepithelial histogenesis or histogenesis from progenitor cells with bilinear differentiation potential? J Pathol. 2005;206(4):451-457. doi:10.1002/path.1797
Hammond MEH, Hayes DF, Wolff AC, Mangu PB, Temin S. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract. 2010;6(4):195-197. doi:10.1200/JOP.777003
Bilous M, Dowsett M, Hanna W, Isola J, Lebeau A, Moreno A, et al. Current perspectives on HER2 testing: a review of national testing guidelines. Mod Pathol. 2003;16(2):173-182.
Wolff AC, Hammond MEH, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013. doi:10.1200/JCO.2013.50.9984
Jalava P, Kuopio T, Juntti-Patinen L, Kotkansalo T, Kronqvist P, Collan Y. Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology. 2006;48(6):674-682. doi:10.1111/j.1365-2559.2006.02402.x
Zar JH. Biostatistical analysis. 5th ed. Prentice-Hall/Pearson; 2010.
Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, Schiff R. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst. 2004; 96(12):926-935. doi:10.1093/jnci/djh166
Ribeiro AS, Sousa B, Carreto B, Mendes N, Nobre AR, Ricardo S, et al. P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model. J Pathol. 2013;229(5):705-718. doi:10.1002/path.4143
Lee JM., Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172(7):973-981. doi:10.1083/jcb.200601018

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