open access

Online first
Original paper
Submitted: 2024-01-21
Accepted: 2024-04-07
Published online: 2024-06-06
Get Citation

The association between integrin β4 overexpression and lymphovascular invasion in papillary thyroid cancer

Busra Tunc Topuz1, Sibel Guldiken2, Ebru Tastekin3, Canberk Topuz3, Mehmet Celik2, Buket Yılmaz Bulbul2, Burak Andac2, Ali Cem Yekdes4
Affiliations
  1. Deparment of Internal Medicine, Medical Faculty, Trakya University, Edirne, Türkiye
  2. Department of Endocrinology and Metabolism, Medical Faculty, Trakya University, Edirne, Türkiye
  3. Department of Medical Pathology, Medical Faculty, Trakya University, Edirne, Türkiye
  4. Department of Public Health, Medical Faculty, Trakya University, Edirne, Türkiye

open access

Online first
Original Paper
Submitted: 2024-01-21
Accepted: 2024-04-07
Published online: 2024-06-06

Abstract

Introduction: Lymphovascular invasion is an independent prognostic marker in papillary thyroid carcinomas. In addition, integrin β4 is associated with advanced progression and metastasis in many malignancies. We aimed to investigate the relationship between integrin β4 and lymphovascular invasion in papillary thyroid carcinoma.

Material and methods: 73 patients with papillary thyroid cancer (48 patients with lymphovascular invasion and 25 patients without) were included in our study. The immunohistochemical staining score for integrin b4 was evaluated according to the percentage and intensity of staining. The staining intensity was scored as 0 (no staining), 1 (weak staining — light yellow), 2 (medium staining — yellow-brown), and 3 (strong staining — brown). The staining was scored by multiplying the percentage and intensity of staining.

Results: The mean percentage of integrin b4 staining was 63.54 ± 22.26% in the group with lymphovascular invasion and 10.2 ± 22.48% in the group without lymphovascular invasion (p < 0.001). When evaluated in terms of staining score, it was found to be 107.08 ± 45.29 in the group with lymphovascular invasion and 16.2 ± 40.03 in the group without lymphovascular invasion (p < 0.001). There was a linear relationship between the percentage of integrin β4 and the staining scores (r² = 0.881; p < 0.001). In the by receiver-operating characteristic (ROC) curve analysis for the cut-off value of the percentage of integrin b4 staining, the area under the curve was found to be 0.916. The cut-off value for the percentage of integrin b4 was found to be 35 (sensitivity 91.7% and specificity 88%) (odds 80.66%).

Conclusions: A significant relationship was found between integrin b4 expression and lymphovascular invasion in papillary thyroid carcinomas. Integrin b4 expression level can be used as a marker to predict the presence of lymphovascular invasion in papillary thyroid carcinomas, especially in large tumours where it may not be possible to sample the entire tumour.

Abstract

Introduction: Lymphovascular invasion is an independent prognostic marker in papillary thyroid carcinomas. In addition, integrin β4 is associated with advanced progression and metastasis in many malignancies. We aimed to investigate the relationship between integrin β4 and lymphovascular invasion in papillary thyroid carcinoma.

Material and methods: 73 patients with papillary thyroid cancer (48 patients with lymphovascular invasion and 25 patients without) were included in our study. The immunohistochemical staining score for integrin b4 was evaluated according to the percentage and intensity of staining. The staining intensity was scored as 0 (no staining), 1 (weak staining — light yellow), 2 (medium staining — yellow-brown), and 3 (strong staining — brown). The staining was scored by multiplying the percentage and intensity of staining.

Results: The mean percentage of integrin b4 staining was 63.54 ± 22.26% in the group with lymphovascular invasion and 10.2 ± 22.48% in the group without lymphovascular invasion (p < 0.001). When evaluated in terms of staining score, it was found to be 107.08 ± 45.29 in the group with lymphovascular invasion and 16.2 ± 40.03 in the group without lymphovascular invasion (p < 0.001). There was a linear relationship between the percentage of integrin β4 and the staining scores (r² = 0.881; p < 0.001). In the by receiver-operating characteristic (ROC) curve analysis for the cut-off value of the percentage of integrin b4 staining, the area under the curve was found to be 0.916. The cut-off value for the percentage of integrin b4 was found to be 35 (sensitivity 91.7% and specificity 88%) (odds 80.66%).

Conclusions: A significant relationship was found between integrin b4 expression and lymphovascular invasion in papillary thyroid carcinomas. Integrin b4 expression level can be used as a marker to predict the presence of lymphovascular invasion in papillary thyroid carcinomas, especially in large tumours where it may not be possible to sample the entire tumour.

Get Citation

Keywords

thyroid cancer; integrin β4; lymphovascular invasion

About this article
Title

The association between integrin β4 overexpression and lymphovascular invasion in papillary thyroid cancer

Journal

Endokrynologia Polska

Issue

Online first

Article type

Original paper

Published online

2024-06-06

Page views

30

Article views/downloads

19

Keywords

thyroid cancer
integrin β4
lymphovascular invasion

Authors

Busra Tunc Topuz
Sibel Guldiken
Ebru Tastekin
Canberk Topuz
Mehmet Celik
Buket Yılmaz Bulbul
Burak Andac
Ali Cem Yekdes

References (33)
  1. Cancer Stat Facts: Thyroid Cancer. http://seer.cancer.gov/statfacts/html/thyro. (08.04.2016).
  2. Perros P, Boelaert K, Colley S, et al. British Thyroid Association. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf). 2014; 81 Suppl 1: 1–122.
  3. Sipos JA, Mazzaferri EL. Thyroid cancer epidemiology and prognostic variables. Clin Oncol (R Coll Radiol). 2010; 22(6): 395–404.
  4. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016; 26(1): 1–133.
  5. Wagner K, Abraham E, Tran B, et al. Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma. ANZ J Surg. 2020; 90(9): 1727–1732.
  6. Pontius LN, Youngwirth LM, Thomas SM, et al. Lymphovascular invasion is associated with survival for papillary thyroid cancer. Endocr Relat Cancer. 2016; 23(7): 555–562.
  7. Kim JM, Kim TY, Kim WB, et al. Lymphovascular invasion is associated with lateral cervical lymph node metastasis in papillary thyroid carcinoma. Laryngoscope. 2006; 116(11): 2081–2085.
  8. Girardi FM, Barra MB, Zettler CG. Variants of papillary thyroid carcinoma: association with histopathological prognostic factors. Braz J Otorhinolaryngol. 2013; 79(6): 738–744.
  9. Sun W, Lan X, Zhang H, et al. Risk Factors for Central Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis. PLoS One. 2015; 10(10): e0139021.
  10. Merdad M, Eskander A, Kroeker T, et al. Predictors of level II and Vb neck disease in metastatic papillary thyroid cancer. Arch Otolaryngol Head Neck Surg. 2012; 138(11): 1030–1033.
  11. Sezer A, Celik M, Yilmaz Bulbul B, et al. Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma. Bosn J Basic Med Sci. 2017; 17(2): 144–151.
  12. Li J, Luo M, Ou H, et al. Integrin β4 promotes invasion and anoikis resistance of papillary thyroid carcinoma and is consistently overexpressed in lymphovascular tumor thrombus. J Cancer. 2019; 10(26): 6635–6648.
  13. Siddharth S, Nayak A, Das S, et al. The soluble nectin-4 ecto-domain promotes breast cancer induced angiogenesis via endothelial Integrin-β4. Int J Biochem Cell Biol. 2018; 102: 151–160.
  14. Masugi Y, Yamazaki K, Emoto K, et al. Upregulation of integrin β4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic ductal adenocarcinoma. Lab Invest. 2015; 95(3): 308–319.
  15. Diaz LK, Cristofanilli M, Zhou X, et al. Beta4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer. Mod Pathol. 2005; 18(9): 1165–1175.
  16. Grossman HB, Lee C, Bromberg J, et al. Expression of the alpha6beta4 integrin provides prognostic information in bladder cancer. Oncol Rep. 2000; 7(1): 13–16.
  17. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017; 67(2): 93–99.
  18. Darren G, Mallery P. SPSS for Windows Step by Step: A Simple Guide and Reference, 17.0 Update (10th ed). , Boston 2010.
  19. Sacks W. Lymphovascular Invasion Is a Predictor of Prognosis for Patients with Well-Differentiated Papillary Thyroid Carcinoma. Clin Thyroidol. 2017; 29(12): 478–481.
  20. Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002; 2(2): 91–100.
  21. Guo W, Giancotti FG. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 2004; 5(10): 816–826.
  22. Giancotti FG, Tarone G. Positional control of cell fate through joint integrin/receptor protein kinase signaling. Annu Rev Cell Dev Biol. 2003; 19: 173–206.
  23. Giancotti FG. Targeting integrin beta4 for cancer and anti-angiogenic therapy. Trends Pharmacol Sci. 2007; 28(10): 506–511.
  24. Mariotti A, Kedeshian PA, Dans M, et al. EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion. J Cell Biol. 2001; 155(3): 447–458.
  25. Trusolino L, Bertotti A, Comoglio PM. A signaling adapter function for alpha6beta4 integrin in the control of HGF-dependent invasive growth. Cell. 2001; 107(5): 643–654.
  26. Guo W, Pylayeva Y, Pepe A, et al. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell. 2006; 126(3): 489–502.
  27. Nikolopoulos SN, Blaikie P, Yoshioka T, et al. Integrin beta4 signaling promotes tumor angiogenesis. Cancer Cell. 2004; 6(5): 471–483.
  28. Sharifi M, Zarrin B, Bahri Najafi M, et al. Integrin α6 β4 on Circulating Tumor Cells of Metastatic Breast Cancer Patients. Adv Biomed Res. 2021; 10: 16.
  29. Ruan S, Lin M, Zhu Y, et al. Integrin β4-Targeted Cancer Immunotherapies Inhibit Tumor Growth and Decrease Metastasis. Cancer Res. 2020; 80(4): 771–783.
  30. Lohi J, Leivo I, Owaribe K, et al. Neoexpression of the epithelial adhesion complex antigens in thyroid tumours is associated with proliferation and squamous differentiation markers. J Pathol. 1998; 184(2): 191–196, doi: 10.1002/(sici)1096-9896(199802)184:2<191::aid-path991>3.0.co;2-s.
  31. Serini G, Trusolino L, Saggiorato E, et al. Changes in integrin and E-cadherin expression in neoplastic versus normal thyroid tissue. J Natl Cancer Inst. 1996; 88(7): 442–449.
  32. Li J, Jiang Yi, Chen C, et al. Integrin β4 Is an Effective and Efficient Marker in Synchronously Highlighting Lymphatic and Blood Vascular Invasion, and Perineural Aggression in Malignancy. Am J Surg Pathol. 2020; 44(5): 681–690.
  33. Kitajiri SI, Hosaka N, Hiraumi H, et al. Increased expression of integrin beta-4 in papillary thyroid carcinoma with gross lymph node metastasis. Pathol Int. 2002; 52(7): 438–441.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via MedicaWydawcą jest  VM Media Group sp. z o.o., Grupa Via Medica, ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl