sdj-10084

Immunohistochemical Expression of PTCH1 and Laminin in Oral Hyperplastic, Premalignant, Squamous Cell Carcinoma and Recurrence Lesions Samples

*Kanar A.  Hamaamin, *Falah A. Hussein, **Dena N. Mohammad

*Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Sulaimani, Sulaimani, Iraq.

**Department of Oral Diagnosis, College of Dentistry, University of Sulaimani, Sulaimani, Iraq.

Submitted: 18/03/2019; Accepted: 23/04/2019; Published 01/06/2019

DOI: https://doi.org/10.17656/sdj.10084

Abstract

Objective: Laminin is a basal membrane glycoprotein that showed progressive loss of continuity from dysplasia to invasive carcinoma. The membranous receptor Patched (PTCH1) promotes the nuclear translocation and activation of the Gli family proteins. The dysregulation of hedgehog signaling reported in various cancers. This study aims to assess the immunohistochemical expression of PTCH1 and laminin in different groups of lesions of oral hyperplastic, premalignant, oral squamous cell carcinoma (OSCC) and recurrence cases.       

Methods: This study involved 35 paraffin blocks of 4 oral hyperplastic, 11 premalignant, 15 OSCC and five recurrences OSCC cases collected from Sulaimani Histopathological Centers. Prepared tissue sections were stained immunohistochemically for both PTCH1 and laminin antibodies and scored. Chi-square correlations used and the p 0.05 considered as statistically significant. 

Results: PTCH1 showed expression in all oral hyperplastic lesions. While 81.8% of oral premalignant lesions demonstrated basal and parabasal distribution with high mixed localization (72.7%), lastly 93.3% of OSCC showed positive expression and mainly found within score 2(46.6%). No significant relations detected between oral hyperplastic and premalignant lesions regarding the expression pattern, localization and intensity as p-values were 0.77, 0.09 and 0.38 respectively. Lastly, the relations between OSCC and recurrent cases to both the expression and localization parameters were non-significant, as p-values were 0.15 and 0.09, respectively. Laminin showed continuous expression at the basement membrane of the normal oral mucosa, while only (50%) of the cases revealed such expression in oral hyperplastic lesions. The oral premalignant lesions expressed 54.5% of a discontinuous pattern. The relation between the oral hyperplastic and premalignant lesions in response to laminin expression was non-significant (P=.21).  A significant relation found in laminin expression between OSCC and recurrence samples (p= 0.02). Finally, a significant correlation found between PTCH1 localization and laminin expression in oral premalignant lesions (p = 0.03).

Conclusions: The PTCH1 overexpression in all of the studied groups of lesions might give an impression of the active role of this biomarker in the progression toward malignancy. Laminin defragmentation, which started from dysplastic lesions extending to OSCC, could emphasize the role of this marker from the early precancerous stage. Furthermore, the combined PTCH1 mixed localization with discontinuous laminin expression might have a significant role in the progression of dysplastic lesions toward cancers. 

                                                                                                                                                                                                                                                                                                                                             

Keywords: PTCH1, Laminin, Oral premalignant lesions, OSCC.                                                                                                                                                                                                                                            Full Article - PDF                                                                                                                                                                                                                                   

                                                                                                                                                                                                                                                                                                                                                   

References:

1. Yardimci G, Kutlubay Z, Engin B, TuzunY. Precancerous lesions of oral mucosa. World J Clin Cases. 2014;16(12):866-72.

2. Rajendran R. Benign and malignant tumors of the oral cavity. In: Rajendran R, Sivapathasundharam B, editors. Shafer's Textbook of Oral Pathology. 6th ed. New Delhi-India: Reed, Elsevier; 2009.p.101. 

3. Sarkis SA, Abdullah BH, Abdul Majeed BA, Talabani NG. Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and  Hamaamin et al. Head Neck Oncol. 2010;2(1):13.

4. Sharma P, Saxena S, Aggarwal P. Trends in the epidemiology of oral squamous cell carcinoma in Western UP. Indian J Dent Res. 2010;21(3):316-19.  

5. Hernandez BY, Zhu X, Goodman MT, Gatewood R, Mendiola P, Quinata K, et al.  Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS ONE. 2017;12(2):e0172196. 

6.  Irani S. Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis. Iran J Pathol. 2016;11(4):303–22. 

7. Tsantoulis PK, Kastrinakis NG, Tourvas AD, Laskaris G, Gorgoulis VG. Advances in the biology of oral cancer. Oral Oncol. 2007;43(6):523-34. 

8. Wilson CW, Chuang PT. Mechanism and evolution of cytosolic Hedgehog signal transduction. Development. 2010;137(13):2079-94. 

9. Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in smallcell lung cancer. Nature. 2003;422(6229):313-17. 

10. Sims–Mourtada J, Izzo JG, Apisarnthanarax S, TehWu T, Malhotra U, Luthra R, et al. Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response. Clin Cancer Res. 2006;12(21):6565-72. 

11. Onishi H, Katano M. Hedgehog signaling pathway as a new therapeutic target in pancreatic cancer. World J Gastroenterol. 2014;20(9):2335-42. 

12. Wang YF, Chang CJ, Lin CP, Chang SY, Chu PY, Tai SK , et al. Expression of Hedgehoge signaling Molecules as a prognostic indicator of oral squamous cell carcinoma. Head neck. 2012;34(11):1556-61. 

13. Shruthy R, Sharada P, Swaminathan U, Nagamalini BR. Immunohistochemical expression of basement membrane laminin in histological grades of oral squamous cell carcinoma:A semiquantitative analysis. J Oral Maxillofac Pathol. 2013;17(2):185-9. 

14. Engbring JA, Kleinman KH. The basement membrane matrix in malignancy. J Pathol. 2003;200(4):465-70. 

15. Yellapurkar S, Natarajan S, Boaz K, Manaktala N, Baliga M, Shetty P ,et al . Expression of Laminin in oral squamous cell carcinomas.  Asian Pac J Cancer Prev. 2018;19(2): 407-13.

16. Souza LF, Souza VF, Silva LD, Santos JN, Reis SR. Expression of basement membrane laminin in oral squamous cell carcinomas. Braz J Otolaryngol. 2007;73(6):768-74. 

17. Kinoshita T, Nohata N, Hanazawa T,  Kikkawa N,  Yamamoto N,  Yoshino H, et al. Tumoursuppressive micro-RNA-29s inhibit cancer cell migration and invasion by targeting lamininintegrin signalling in head and neck squamous cell carcinoma. Br J Cancer. 2013;109(10):2636-45.  

18. Degen M, Natarajan E, Barron P, Widlund HR, Rheinwald JG. MAPK/Erk dependent translation factor hyper activation and dysregulated Laminin γ2 expression in oral dysplasia  and squamous cell carcinoma. Am J Pathol. 2012;180(6):2462-78. 

19. García SA, Abad-Hernández MM, FonsecaSánchez E, Julián -Gonzalez R, Galindo-Villardón P, Cruz-Hernández JJ, et al . E-cadherin, laminin and collagen IV expression in the evo-lution from dysplasia to oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal. 2006;11(2):E100-5. 

20. Abdel Rahman GA, El Bolok AH, Essa TE. Immunohistochemical expression of laminin-5γ2 in oral squamous cell carcinoma. Egypt Dent. J. 2015;61(3):3535-39. 

21. Yang L, Wang LS, Chen XL, Gatalica Z, Qiu S, Liu Z, et al. Hedgehog signaling activation in the development of squamous cell carcinoma and adenocarcinoma of esophagus. Int J Biochem Mol Biol. 2012;3(1):46-57. 

22. Kobayashi Y, Nakajima T, Saku T. Loss of basement membranes in the invading front oral squamous cell carcinoma with high potential of lymph node metastasis: An immunohistochemical study for laminin and type IV collagen. Pathol Int. 1995;45(5):327-34.

23. Dias RB, Valverde Lde F, Sales CB, Guimarães VS, Cabral MG, de Aquino Xavier FC, et al. Enhanced  expression   of  hedgehog  pathway protiens in oral epithelial dysplasia. Appl Immunohistochem Mol Morphol. 2016;24(8):595-602. 

24. Leovic D, Sabol M, Ozretic P, Musani V, Car D, Marjanovic K, et al. Hh-Gli signaling pathway activity in oral and oropharyngeal squamous cell carcinoma. Head Neck. 2012;34(1):104-12. 

25. Srinath S, Iyengar AR, Mysorekar V. Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study. J Oral Maxillofac Pathol. 2016;20(3):377-83. 

26. Firth NA, Reade PC. The prognosis of oral mucosal squamous cell carcinomas: a comparison of clinical and histopathological grading and of laminin and type IV collagen staining. Austr Dent J. 1996;41(2):83-6. 

27. Kannan S, Balaram P, Chandran GJ, Pillai MR, Mathew B, Nalinakumari KR, et al . Alterations in expression of basement membrane proteins during tumor progression in oral mucosae. Histopathol. 1994;24(6):531-7. 

28. Rani V, McCullough M, Chandu A. Assessment of laminin-5 in oral dysplasia and squamous cell carcinoma. J Oral Maxillofac Surg. 2013;71(11):1873-9. 

29. Mostafa WZ, Mahfouz SM, Bosseila M, Sobhi RM, Zaki NS. An Immunohistochemical study of laminin in cutaneous and mucosal squamous cell carcinomas. J Egypt Women Dermatol Soc. 2007;4:24-33. 

30. Stoltzfus P, Högmo A, Lindholm J, Aspenblad U, Auer G, Munck-Wikland E. The gamma2 chain of laminin-5 as an indicator of increased risk for recurrence in T1 stage tongue cancer. Anticancer Res. 2004;24(5B):3109-14.

 

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