Expression of CD9 and CD82 in papillary thyroid microcarcinoma and its prognostic significance
Abstract
Introduction: papillary thyroid microcarcinoma is a well-known malignant neoplasm with good prognosis. The known prognostic factors are patient’s age, multifocality, and extrathyroidal extension. CD9 and CD82, members of the tetraspanin family, are expressed in numerous cancer cells and play many roles associated with the cellular process.
Material and methods: we investigated the immunohistochemical expression of CD9 and CD82 in papillary thyroid microcarcinoma and analysed the clinicopathological and prognostic significance. For the retrospective analysis, we collected the cases of 553 PTMC patients who had undergone thyroidectomy.
Results: The group with lymph node metastasis showed higher immunostaining intensity for CD9 than the group without metastasis (p = 0.002). In multivariate analysis, high CD9 intensity (OR = 1.58 in 3+, p = 0.0025) correlated with lymph node metastasis.
Conclusion: We suggest CD9 as a predictive prognostic factor for lymph node metastasis in PTMC.
Keywords: CD9CD82prognosispapillary thyroid microcarcinoma
References
- Hay ID, Hutchinson ME, Gonzalez-Losada T, et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery. 2008; 144(6): 980–987.
- Yoon JH, Lee HS, Kim EK, et al. Short-term Follow-up US Leads to Higher False-positive Results Without Detection of Structural Recurrences in PTMC. Medicine (Baltimore). 2016; 95(1): e2435.
- Siddiqui S, White MG, Antic T, et al. Clinical and Pathologic Predictors of Lymph Node Metastasis and Recurrence in Papillary Thyroid Microcarcinoma. Thyroid. 2016; 26(6): 807–815.
- Shi C, Guo Y, Lv Y, et al. Clinicopathological Features and Prognosis of Papillary Thyroid Microcarcinoma for Surgery and Relationships with the BRAFV600E Mutational Status and Expression of Angiogenic Factors. PLoS One. 2016; 11(12): e0167414.
- Lim DJ, Baek KH, Lee YS, et al. Clinical, histopathological, and molecular characteristics of papillary thyroid microcarcinoma. Thyroid. 2007; 17(9): 883–888.
- Boucheix C, Duc GH, Jasmin C, et al. Tetraspanins and malignancy. Expert Rev Mol Med. 2001; 2001: 1–17.
- Lee J, Byun HJ, Lee MS, et al. The metastasis suppressor CD82/KAI1 inhibits fibronectin adhesion-induced epithelial-to-mesenchymal transition in prostate cancer cells by repressing the associated integrin signaling. Oncotarget. 2017; 8(1): 1641–1654.
- Zhang BH, Liu W, Li L, et al. KAI1/CD82 and MRP1/CD9 serve as markers of infiltration, metastasis, and prognosis in laryngeal squamous cell carcinomas. Asian Pac J Cancer Prev. 2013; 14(6): 3521–3526.
- Wu Q, Yang Y, Wu S, et al. Evaluation of the correlation of KAI1/CD82, CD44, MMP7 and β-catenin in the prediction of prognosis and metastasis in colorectal carcinoma. Diagn Pathol. 2015; 10: 176.
- Chen Z, Mustafa T, Trojanowicz B, et al. CD82, and CD63 in thyroid cancer. Int J Mol Med. 2004; 14(4): 517–527.
- Kwon HJ, Min SY, Park MJ, et al. Expression of CD9 and CD82 in clear cell renal cell carcinoma and its clinical significance. Pathol Res Pract. 2014; 210(5): 285–290.
- Jazdzewski K, Boguslawska J, Jendrzejewski J, et al. Thyroid hormone receptor beta (THRB) is a major target gene for microRNAs deregulated in papillary thyroid carcinoma (PTC). J Clin Endocrinol Metab. 2011; 96(3): E546–E553.
- Master A, Wójcicka A, Piekiełko-Witkowska A, et al. Untranslated regions of thyroid hormone receptor beta 1 mRNA are impaired in human clear cell renal cell carcinoma. Biochim Biophys Acta. 2010; 1802(11): 995–1005.
- Regina Todeschini A, Hakomori Si. Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim Biophys Acta. 2008; 1780(3): 421–433.
- Lazo PA. Functional implications of tetraspanin proteins in cancer biology. Cancer Sci. 2007; 98(11): 1666–1677.
- Kim KJ, Kwon HJ, Kim MC, et al. CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance. J Pathol Transl Med. 2016; 50(6): 459–468.
- Dong T, Liu Z, Zhao S, et al. The Expression of CD9 and PIK3CD is Associated with Prognosis of Follicular Lymphoma. J Cancer. 2015; 6(12): 1222–1229.
- Huang CI, Kohno N, Ogawa E, et al. Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. Am J Pathol. 1998; 153(3): 973–983.
- Houle CD, Ding XY, Foley JF, et al. Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression. Gynecol Oncol. 2002; 86(1): 69–78.
- Chen Z, Gu S, Trojanowicz B, et al. Down-regulation of TM4SF is associated with the metastatic potential of gastric carcinoma TM4SF members in gastric carcinoma. World J Surg Oncol. 2011; 9: 43.
- Yin M, Soikkeli J, Jahkola T, et al. Osteopontin promotes the invasive growth of melanoma cells by activating integrin αvβ3 and down-regulating tetraspanin CD9. Am J Pathol. 2014; 184(3): 842–858.
- Charrin S, le Naour F, Silvie O, et al. Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J. 2009; 420(2): 133–154.
- Murayama Y, Shinomura Y, Oritani K, et al. The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells. J Cell Physiol. 2008; 216(1): 135–143.
- Castro-Sanchez L, Soto-Guzman A, Navarro-Tito N, et al. Native type IV collagen induces cell migration through a CD9 and DDR1-dependent pathway in MDA-MB-231 breast cancer cells. Eur J Cell Biol. 2010; 89(11): 843–852.
- Yamaguchi H, Wyckoff J, Condeelis J. Cell migration in tumors. Curr Opin Cell Biol. 2005; 17(5): 559–564.
- Iwasaki T, Takeda Y, Maruyama K, et al. Deletion of tetraspanin CD9 diminishes lymphangiogenesis in vivo and in vitro. J Biol Chem. 2013; 288(4): 2118–2131.
- Kamisasanuki T, Tokushige S, Terasaki H, et al. Targeting CD9 produces stimulus-independent antiangiogenic effects predominantly in activated endothelial cells during angiogenesis: a novel antiangiogenic therapy. Biochem Biophys Res Commun. 2011; 413(1): 128–135.
- Richardson MM, Jennings LK, Zhang XA. Tetraspanins and tumor progression. Clin Exp Metastasis. 2011; 28(3): 261–270.
- Huang CL, Ueno M, Liu D, et al. MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2. Oncogene. 2006; 25(49): 6480–6488.
- Takenawa T, Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. 2007; 8(1): 37–48.
- Tang M, Yin G, Wang F, et al. Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface. Oncol Rep. 2015; 34(1): 350–358.
- Hwang JR, Jo K, Lee Y, et al. Upregulation of CD9 in ovarian cancer is related to the induction of TNF-α gene expression and constitutive NF-κB activation. Carcinogenesis. 2012; 33(1): 77–83.
- Xuan H, Hu X, Huang J. Role of motility-related protein-1 in promoting the development of several types of cancer (Review). Oncol Lett. 2014; 7(3): 611–615.
- Tang Y, Bhandaru M, Cheng Y, et al. The role of the metastasis suppressor gene KAI1 in melanoma angiogenesis. Pigment Cell Melanoma Res. 2015; 28(6): 696–706.
- Ito Y, Yoshida H, Uruno T, et al. KAI1 expression in thyroid neoplasms: its linkage with clinicopathologic features in papillary carcinoma. Pathol Res Pract. 2003; 199(2): 79–83.
- Risinger JI, Custer M, Feigenbaum L, et al. Normal viability of Kai1/Cd82 deficient mice. Mol Carcinog. 2014; 53(8): 610–624.
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