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Tumor Biology

, Volume 37, Issue 5, pp 6185–6190 | Cite as

Wnt5a and Ror2 expression associate with the disease progress of primary thyroid lymphoma

  • Lei Wang
  • Dong Yang
  • Ying-Hou Wang
  • Xi Li
  • Hong-Ming Gao
  • Jun-Yuan Lv
  • Lei Wang
  • Shi-Jie Xin
Research Article

Abstract

Primary thyroid lymphoma (PTL) is a rare malignant thyroid tumor; its pathogenesis is closely related to chronic lymphocytic thyroiditis. The different pathological subtypes and stages of PTL have distinct clinical characteristics and prognosis, but the specific reasons are not clear. Wnt5a is a representative protein of non-canonical Wnt signaling. It plays an important role in many different types of tumors. This study is to explore the changes of Wnt5a and its receptor Ror2 in PTL development process and the clinical significance of their represent. We collected 22 PTL patient tumor specimens and clinical data. We observed the expression of Wnt5a and Ror2 in PTL tumor tissues by immunohistochemistry. Wnt5a was expressed positively in 12 (54.5 %) cases, and Ror2 was expressed positively in 18 (81.8 %) cases. The expression of Wnt5a had a significant difference in different pathological subtypes of PTL (P < 0.05). Wnt5a and Ror2 expression were associated with local invasion and clinical stage, respectively (P < 0.05), and had no significant correlation with age, gender, and tumor size. Although, no significant difference in overall survival was found between positive and negative groups of Wnt5a (P = 0.416) or Ror2 (P = 0.256), respectively. We still consider that Wnt5a and Ror2 play a complex and subtle role in the pathogenesis and progression of PTL and may become potential biomarkers and therapeutic targets of PTL.

Keywords

Primary thyroid lymphoma Wnt5a Ror2 Immunohistochemistry 

Notes

Acknowledgments

This research was funded by the National Natural Science Foundation of China (No.81170295 and 81000136) and the Foundation of Liaoning Provincial Science and Technology Department (2013225086).

Conflicts of interest

None

References

  1. 1.
    Ansell SM, Grant CS, Habermann TM. Primary thyroid lymphoma. Semin Oncol. 1999;26:316–23.PubMedGoogle Scholar
  2. 2.
    Pedersen RK, Pedersen NT. Primary non-Hodgkin’s lymphoma of the thyroid gland: a population based study. Histopathology. 1996;28(1):25–32.CrossRefPubMedGoogle Scholar
  3. 3.
    Hwang YC, Kim TY, Kim WB, et al. Clinical characteristics of primary thyroid lymphoma in Koreans. Endocr J. 2009;56(3):399–405.CrossRefPubMedGoogle Scholar
  4. 4.
    Graff-Baker A, Roman SA, Thomas DC. Prognosis of primary thyroid lymphoma: demographic, clinical and pathologic predictors of survival in 1408 cases. Surgery. 2009;146(6):1105–15.CrossRefPubMedGoogle Scholar
  5. 5.
    Widder S, Pasieka JL. Primary thyroid lymphomas. Curr Treat Options Oncol. 2004;5:307–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Kossev P, Livolsi V. Lymphoid lesions of the thyroid: review in light of the revised European American lymphoma classification and upcoming World Health Organization classification. Thyroid. 1999;9:1273–80.CrossRefPubMedGoogle Scholar
  7. 7.
    Katna R, Shet T, Sengar M. Clinicopathologic study and outcome analysis of thyroid lymphomas: experience from a tertiary cancer center. Head Neck. 2013;35(2):165–71.CrossRefPubMedGoogle Scholar
  8. 8.
    Sakorafas GH, Kokkoris P, Farley DR. Primary thyroid lymphoma (correction of lympoma): diagnostic and therapeutic dilemmas. Surg Oncol. 2010;19(4):e124–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Cha H, Kim JW, Suh CO. Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study. Radiat Oncol J. 2013;31(4):177–84.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ruggiero FP, Frauenhoffer E, Stack BC. Thyroid lymphoma: a single institution’s experience. Otolaryngol Head Neck Surg. 2005;133:888–96.CrossRefPubMedGoogle Scholar
  11. 11.
    Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.CrossRefPubMedGoogle Scholar
  12. 12.
    Verkaar F, Zaman GJ. A model for signaling specificity of Wnt/Frizzled combinations through co-receptor recruitment. FEBS Lett. 2010;584(18):3850–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Pukrop T, Klemm F, Hagemann T, et al. Wnt5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci U S A. 2006;103:5454–9.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    O’Connell MP, Fiori JL, Xu M, et al. The orphan tyrosine kinase receptor, Ror2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 2010;29:34–44.CrossRefPubMedGoogle Scholar
  15. 15.
    Ripka S, Konig A, Buchholz M, et al. WNT5A—target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer. Carcinogenesis. 2007;28:1178–87.CrossRefPubMedGoogle Scholar
  16. 16.
    Yamamoto H, Kitadai Y, Yamamoto H, et al. Laminin gamma2 mediates Wnt5a-induced invasion of gastric cancer cells. Gastroenterology. 2009;137(1):242–52. 252.e1-6.CrossRefPubMedGoogle Scholar
  17. 17.
    Enomoto M, Hayakawa S, Itsukushima S, et al. Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling. Oncogene. 2009;28(36):3197–208.CrossRefPubMedGoogle Scholar
  18. 18.
    He F, Xiong W, Yu X, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development. 2008;135:3871–9.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    McDonald SL, Silver A. The opposing roles of Wnt-5a in cancer. Br J Cancer. 2009;101(2):209–14.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kremenevskaja N, von Wasielewski R, Rao AS, et al. Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene. 2005;24(13):2144–54.CrossRefPubMedGoogle Scholar
  21. 21.
    Han X, Kilfoy B, Zheng T, et al. Lymphoma survival patterns by WHO subtype in the United States, 1973–2003. Cancer Causes Control. 2008;19:841–58.CrossRefPubMedGoogle Scholar
  22. 22.
    Thieblemont C, Mayer A, Dumontet C, et al. Primary thyroid lymphoma is a heterogeneous disease. J Clin Endocrinol Metab. 2002;87(1):105–11.CrossRefPubMedGoogle Scholar
  23. 23.
    Grivennikov SI, Karin M. Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev. 2010;20(1):65–71.CrossRefPubMedGoogle Scholar
  24. 24.
    Mikels AJ, Nusse R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 2006;4(4):e115.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kim J, Kim DW, Chang W, et al. Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-κB-B cell lymphoma 6 signaling. J Immunol. 2012;188(1):182–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Lee JM, Kim IS, Kim H, et al. RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer. Mol Cell. 2010;37(2):183–95.CrossRefPubMedGoogle Scholar
  27. 27.
    Topol L, Jiang X, Choi H, et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation. J Cell Biol. 2003;162(5):899–908.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Sato A, Yamamoto H, Sakane H, et al. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29(1):41–54.CrossRefPubMedGoogle Scholar
  29. 29.
    Blanc E, Roux GL, Bénard J, et al. Low expression of Wnt-5a gene is associated with high-risk neuroblastoma. Oncogene. 2005;24(7):1277–83.CrossRefPubMedGoogle Scholar
  30. 30.
    Leris AC, Roberts TR, Jiang WG, et al. WNT5A expression in human breast cancer. Anticancer Res. 2005;25(2A):731–4.PubMedGoogle Scholar
  31. 31.
    Weeraratna AT, Jiang Y, Hostetter G, et al. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 2002;1(3):279–88.CrossRefPubMedGoogle Scholar
  32. 32.
    Da Forno PD, Pringle JH, Hutchinson P, et al. WNT5A expression increases during melanoma progression and correlates with outcome. Clin Cancer Res. 2008;14(18):5825–32.CrossRefPubMedGoogle Scholar
  33. 33.
    Liang H, Chen Q, Coles AH, et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell. 2003;4(5):349–60.CrossRefPubMedGoogle Scholar
  34. 34.
    Nishita M, Yoo SK, Nomachi A, et al. Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration. J Cell Biol. 2006;175(4):555–62.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yamamoto S, Nishimura O, Misaki K, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15(1):23–36.CrossRefPubMedGoogle Scholar
  36. 36.
    Grumolato L, Liu G, Mong P, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24(22):2517–30.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Wright TM, Brannon AR, Gordan JD, et al. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene. 2009;28(27):2513–23.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Chang C, Werb Z. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 2001;11(11):S37–43.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Lei Wang
    • 1
  • Dong Yang
    • 1
  • Ying-Hou Wang
    • 2
  • Xi Li
    • 1
  • Hong-Ming Gao
    • 1
  • Jun-Yuan Lv
    • 1
  • Lei Wang
    • 1
  • Shi-Jie Xin
    • 1
  1. 1.Department of Vascular and Thyroid Surgery, the First Affiliated HospitalChina Medical UniversityShenyangChina
  2. 2.Department of General SurgeryNO.202 Hospital of PLAShenyangChina

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