EXPRESSIONS OF IGF-1R, EZH2, LAMININ-5 IN LEUKOPLAKIA AND ORAL SQUAMOUS CELL CARCINOMA

Abstract

ABSTRACT Aim: The aim of this study is to investigate the expressions of IGF-1R, EZH2 and Laminin-5 antibodies in biopsy samples of leukoplakia and squamous cell carcinoma of the oral mucosa by immunohistochemistry method. Materials and Methods: The study consisted of three groups; oral squamous cell carcinoma leukoplakia and control groups. The control group consisted of lesions with oral fibrous hyperplasia diagnosis. Biopsies of 38 patients for oral squamous cell carcinoma, 32 patients for leukoplakia and 15 patients for control group were examined and evaluated degree of staining of antibodies. Antibodies were evaluated as negative (0-10%):0, 1 positive (11-30%):+, 2 positive (31-60%):++, 3 positive (61-100%):+++ according to staining percentages. The staining degrees of antibodies were compared with Mann Whitney U test in study and control groups. Gender distribution between groups was compared with LSD test and SPSS 21 program was used for calculations. The results were statistically significancant is p ˂0.05. Results: According to the findings obtained in this study antibodies revealed significantly higher staining in the oral squamous cell carcinoma group and leukoplakia group compared to with control groups. Conclusion: In this study, it was shown that EZH2, IGF-1R and Laminin-5 may have roles in cancer development. Key words: Squamous cell carcinoma, leukoplakia LÖKOPLAKİ VE ORAL SKUAMÖZ HÜCRELİ KARSİNOMDA IGF-1R, EZH2, LAMININ-5 EKSPRESYONU ÖZET Amaç:. Çalışmanın amacı oral mukozada lökoplaki ve skuamöz hücreli karsinom biyopsi örneklerinde IGF-1R, EZH2 ve Laminin-5 antikorlarının immünhistokimyasal methodla ekspresyonlarının araştırılmasıdır. Gereç ve Yöntem: Çalışmayı oral skuamöz hücreli karsinom, lökoplaki ve kontrol grubu olmak üzere üç grup oluşturmaktadır. Kontrol grubunu oral fibröz hiperplazi tanılı lezyonlar oluşturmuştur. Oral skuamöz hücreli karsinomda 38, lökoplakide 32 ve kontrol grubunda 15 biyopsi örneğinde IGF-1R, EZH2 ve Laminin-5 antikorlarının boyanma dereceleri incelendi ve değerlendirildi. Antikorlar boyanma yüzdelerine göre negatif (%0-10):0, 1 pozitif (%11-30):+, 2 pozitif (%31-60):++, 3 pozitif (%61-100):+++ olarak değerlendirildi. Çalışma ve kontrol gruplarında EZH2, IGF-1R ve Laminin-5 antikorları ile boyanma dereceleri Mann Whitney U testiyle karşılaştırılmıştır. Gruplar arasındaki cinsiyet dağılımı karşılaştırılması LSD (Least Significant Difference) testiyle, hesaplamalar SPSS 21 programıyla yapılmıştır. Anlamlılık sınırı p˂0.05tir. Bulgular: Bu çalışmada elde edilen bulgulara göre IGF-1R, EZH2 ve Laminin-5 antikorlarının kontrol grubuyla karşılaştırıldığında lökoplaki ve oral skuamöz hücreli karsinom gruplarında önemli derecede yüksek boyanma göstermiştir. Sonuç: Bu çalışmada EZH2, IGF-1R ve Laminin-5'in kanser gelişiminde rolleri olabileceği gösterilmiştir. Anahtar Kelimeler: Skuamöz hücreli karsinom, lökoplaki

Keywords

• Squamous cell carcinoma
• leukoplakia
• Skuamöz hücreli karsinom

EXPRESSIONS OF IGF-1R, EZH2, LAMININ-5 IN LEUKOPLAKIA AND ORAL SQUAMOUS CELL CARCINOMA

Abstract

ABSTRACT Aim: The aim of this study is to investigate the expressions of IGF-1R, EZH2 and Laminin-5 antibodies in biopsy samples of leukoplakia and squamous cell carcinoma of the oral mucosa by immunohistochemistry method. Materials and Methods: The study consisted of three groups; oral squamous cell carcinoma leukoplakia and control groups. The control group consisted of lesions with oral fibrous hyperplasia diagnosis. Biopsies of 38 patients for oral squamous cell carcinoma, 32 patients for leukoplakia and 15 patients for control group were examined and evaluated degree of staining of antibodies. Antibodies were evaluated as negative (0-10%):0, 1 positive (11-30%):+, 2 positive (31-60%):++, 3 positive (61-100%):+++ according to staining percentages. The staining degrees of antibodies were compared with Mann Whitney U test in study and control groups. Gender distribution between groups was compared with LSD test and SPSS 21 program was used for calculations. The results were statistically significancant is p ˂0.05. Results: According to the findings obtained in this study antibodies revealed significantly higher staining in the oral squamous cell carcinoma group and leukoplakia group compared to with control groups. Conclusion: In this study, it was shown that EZH2, IGF-1R and Laminin-5 may have roles in cancer development. Key words: Squamous cell carcinoma, leukoplakia LÖKOPLAKİ VE ORAL SKUAMÖZ HÜCRELİ KARSİNOMDA IGF-1R, EZH2, LAMININ-5 EKSPRESYONU ÖZET Amaç:. Çalışmanın amacı oral mukozada lökoplaki ve skuamöz hücreli karsinom biyopsi örneklerinde IGF-1R, EZH2 ve Laminin-5 antikorlarının immünhistokimyasal methodla ekspresyonlarının araştırılmasıdır. Gereç ve Yöntem: Çalışmayı oral skuamöz hücreli karsinom, lökoplaki ve kontrol grubu olmak üzere üç grup oluşturmaktadır. Kontrol grubunu oral fibröz hiperplazi tanılı lezyonlar oluşturmuştur. Oral skuamöz hücreli karsinomda 38, lökoplakide 32 ve kontrol grubunda 15 biyopsi örneğinde IGF-1R, EZH2 ve Laminin-5 antikorlarının boyanma dereceleri incelendi ve değerlendirildi. Antikorlar boyanma yüzdelerine göre negatif (%0-10):0, 1 pozitif (%11-30):+, 2 pozitif (%31-60):++, 3 pozitif (%61-100):+++ olarak değerlendirildi. Çalışma ve kontrol gruplarında EZH2, IGF-1R ve Laminin-5 antikorları ile boyanma dereceleri Mann Whitney U testiyle karşılaştırılmıştır. Gruplar arasındaki cinsiyet dağılımı karşılaştırılması LSD (Least Significant Difference) testiyle, hesaplamalar SPSS 21 programıyla yapılmıştır. Anlamlılık sınırı p˂0.05tir. Bulgular: Bu çalışmada elde edilen bulgulara göre IGF-1R, EZH2 ve Laminin-5 antikorlarının kontrol grubuyla karşılaştırıldığında lökoplaki ve oral skuamöz hücreli karsinom gruplarında önemli derecede yüksek boyanma göstermiştir. Sonuç: Bu çalışmada EZH2, IGF-1R ve Laminin-5'in kanser gelişiminde rolleri olabileceği gösterilmiştir. Anahtar Kelimeler: Skuamöz hücreli karsinom, lökoplaki

Keywords

• Squamous cell carcinoma
• leukoplakia
• Skuamöz hücreli karsinom

References

1. 1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009;45(4-5):309-316
2. 2. Pan H, Gu L, Liu B, Li Y, Wang Y, Bai X, Li L, Wang B, Peng Q, Yao Z, Tang Z. Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma. PLos One 2017;12(2):e0168900
3. 3. Akmansoy BP, Pekiner FN, Şakır MD, Alatlı C. Oral Skuamöz Hücreli Karsinom: 3 Olgu Sunumu ve Literatür Derlemesi. Atatürk Üniv Diş Hek Fak Derg 2018;28(2):239-244
4. 4. Chaudhari V, Pradeep GL, Prakash N, Mahajan AM. Estimation of salivary sialic acid in oral premalignancy and oral squamous cell carcinoma. Contemp Clin Dent 2016;7(4):451-456
5. 5. Bewley AF, Farwell DG. Oral leukoplakia and oral cavity squamous cell carcinoma Clin Dermatol 2017;35(5):461-467
6. 6. Ramya AS, Majumdar S, Babu TM, Uppala D, Srinivas B, Rao AK. Expression of humanpapillomavirus DNA and p53 polymorphisms through polymerase chain reaction in normal mucosa and oral leukoplakia individuals with deleterious oral habits Int J Appl Basic Med Res 2017;7(2):134-138
7. 7. Kidani K, Osaki M, Tamura T, Yamaga K, Shomori K, Ryoke K, Ito H. High expression of EZH2 is associated with tumor proliferation and prognosis in human oral squamous cell carcinomas. Oral Oncol 2009;45(1):39-46
8. 8. Sun Y, Sun X, Shen B. Molecular imaging of IGF-1R in cancer. Mol Imaging 2017;16:1-7

9. 9. An SJ, Lin QX, Chen ZH, Su J, Cheng H, Xie Z, Zhang XC, Zhou HY, Huang Y, Chen SL, Guo WB, Wu YL. Combinations of laminin-5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer. Exp Ther Med 2012;4(2):226-230
10. 10. Zeng J, Kirk BD, Gou Y, Wang Q, Ma J. Genome-wide polycomb target gene prediction in Drosophila melanogaster. Nucleic Acids Res 2012;40:5848-63
11. 11. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RGAB, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 2003;100:11606-611
12. 12. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RGAB, Otte AP, Rubin MA, Chinnaiyan AM. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002; 419:624-29
13. 13. Hinz S, Kempkensteffen C, Christoph F, Hoffmann M, Krause H, Schrader M, Schostak M, Miller K, Weikert S. Expression of polycomb group protein EZH2 and its relation to outcome in patients with urothelial carcinoma of the bladder. J Cancer Res Clin Oncol 2008;134(3):331-6
14. 14. Dziadziuszko R, Camidge DR, Hirsch FR. The insulin-like growth factor pathway in lung cancer. J Thorac Oncol 2008;3(8):815-8
15. 15. Xiong L, Kou F, Yang Y, Wu J. A novel role for IGF-1R in p-53 mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop. J Cell Biol 2007;178(6):995-1007
16. 16. Brady G, Crean SJ, Naik P, Kapas S. Upregulation of IGF-2 and IGF-1 receptor expression in oral cancer cell lines. Int J Oncol 2007;31(4):875-81
17. 17. Larsson O, Girnita A, Girnita L. Role of insulin-like growth factor 1 receptor signalling in cancer. Br J Cancer 2005;92(12):2097-101
18. 18. Leroith D, Roberts Jr CT. The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127-137
19. 19. Barnes CJ, Ohshiro K, Rayala SK, El-Naggar AK, Kumar R. Insulin-like growth factor receptor as a therapeutic target in head and neck cancer. Clin Cancer Res 2007;13(14):4291-99
20. 20. Slomiany MG, Black LA, Kibbey MM, Tingler MA, Day TA, Rosenzweig SA. Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma. Cancer Lett 2007;248(2):269-79
21. 21. Papadimitrakopoulou VA, Brown EN, Liu DD, El-Naggar AK, Jack Lee J, Hong WK, Lee HY. The prognostic role of loss of insulin-like growth factor-binding protein-3 expression in head and neck carcinogenesis. Cancer Lett 2006;239(1):136-143
22. 22. Reszec J, Duraj E, Koda M, Musiatowicz B, Sulkowska M. Insulin-like growth factor-1 receptor in human oral cancer. Rocz Akad Med Bialymst 2004;49:58-60
23. 23. Lara PC, Bordon E, Rey A, Moreno M, Lloret M, Henriquez-Hernandez LA. IGF-1R expression predicts clinical outcome in patients with locally advanced oral squamous cell carcinoma. Oral Oncol 2011;47(7):615-19
24. 24. Sonnenberg A, de Melker AA, Martinez de Velasco AM, Janssen H, Calafat J, Niessen CM. Formation of hemidesmosomes in cells of a transformed murine mammary tumor cell line and mechanisms involved in adherence of these cells to laminin and kalinin. J Cell Sci 1993;106:1083-102
25. 25. Goldfinger LE, Hopkinson SB, deHart GW, Collawn S, Couchman JR, Jones JC. The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and skin. J Cell Sci 1999;112:2615-29
26. 26. Zhang K, Kramer RH. Laminin 5 deposition promotes keratinocyte motility. Exp Cell Res 1996;227:309-22
27. 27. Pyke C, Romer J, Kallunki P, Lund LR, Ralfkiaer E, Dano K, Tryggvason K. The gamma2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers. Am J Pathol 1994; 145(4):782-91
28. 28. Pyke C, Salo S, Ralfkiaer E, Romer J, Dano K, Tryggvason K. Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas. Cancer Res 1995;55(18):4132-39
29. 29. Sordat I, Bosman FT, Dorta G, Rousselle P, Aberdam D, Blum AL, Sordat B. Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia. J Pathol 1998;185(1):44-52
30. 30. Imura J, Uchida Y, Nomoto K, Ichikawa K, Tomita S, Iijima T, Fujimori T. Laminin-5 is a biomarker of invasiveness in cervical adenocarcinoma. Diagn P 2012;7:105
31. 31. Rani V, McCullough M, Chandu A. Assesment of laminin-5 in oral dysplasia and squamous cell carcinoma. J Oral Maxillofac Surg 2013;71:1873-79