El-naggar, H., El Nouaem, M., Darwish, Z., Swaify, G., Essawy, M. (2021). ROLE OF MYOFIBROBLASTS IN THE PRIMARY LESIONS AND LYMPH NODE METASTASIS OF ORAL SQUAMOUS CELL CARCINOMA. Alexandria Dental Journal, 46(3), 78-84. doi: 10.21608/adjalexu.2021.165446
Hagar Alaaudien El-naggar; Manal I. El Nouaem; Zeinab E. Darwish; Gamal A. Swaify; Marwa M. Essawy. "ROLE OF MYOFIBROBLASTS IN THE PRIMARY LESIONS AND LYMPH NODE METASTASIS OF ORAL SQUAMOUS CELL CARCINOMA". Alexandria Dental Journal, 46, 3, 2021, 78-84. doi: 10.21608/adjalexu.2021.165446
El-naggar, H., El Nouaem, M., Darwish, Z., Swaify, G., Essawy, M. (2021). 'ROLE OF MYOFIBROBLASTS IN THE PRIMARY LESIONS AND LYMPH NODE METASTASIS OF ORAL SQUAMOUS CELL CARCINOMA', Alexandria Dental Journal, 46(3), pp. 78-84. doi: 10.21608/adjalexu.2021.165446
El-naggar, H., El Nouaem, M., Darwish, Z., Swaify, G., Essawy, M. ROLE OF MYOFIBROBLASTS IN THE PRIMARY LESIONS AND LYMPH NODE METASTASIS OF ORAL SQUAMOUS CELL CARCINOMA. Alexandria Dental Journal, 2021; 46(3): 78-84. doi: 10.21608/adjalexu.2021.165446
ROLE OF MYOFIBROBLASTS IN THE PRIMARY LESIONS AND LYMPH NODE METASTASIS OF ORAL SQUAMOUS CELL CARCINOMA
1oral pathology - Faculty of dentistry - Alexandria university
2Professor of Oral Pathology. Oral pathology Department, Faculty of Dentistry, Alexandria University.
3Professor of Cranio-Maxillofacial and Plastic Surgery Department, Faculty of Dentistry, Alexandria University.
4Fellow of Oral Pathology Department, Faculty of Dentistry, Alexandria University.
Abstract
physiologic and pathologic processes such as wound healing and tumorigenesis, respectively. Tumor cells work in close coordination with stromal elements from its stage of emergence to metastasis. Myofibroblasts are important stromal cells that play a crucial role in carcinogenesis due to its ability to modify the extracellular matrix. Alpha smooth muscle actin (α-SMA) is regarded as the most widely used biomarker for identifying myofibroblasts. The presence of myofibroblasts has been demonstrated in various malignant lesions. However, the number of studies evaluating their role in oral squamous cell carcinoma (OSCC) remains limited. OBJECTIVES: The present study aimed to assess the presence and distribution patterns of myofibroblasts in OSCC primary tissues according to histological grade, as well as to determine its correlation with metastasis in regional lymph nodes (LNs). MATERIAL AND METHODS: Immunohistochemical study using the α-SMA antibody was done on 30 OSCC cases (15 cases with LN metastasis and 15 cases without LN metastasis) and 15 normal oral mucosal tissues. RESULTS: Most of OSCC tissues showed positive immunoreactivity to α-SMA, while normal tissues were immune-negative. The expression of α-SMA was significantly higher in the OSCC with LN metastasis than OSCC without LN metastasis (P < 0.05). Conversely, there was no significant correlation with the histological grades of OSCC. CONCLUSION: α-SMA could be used as a monitory marker in OSCC.
1. Irimie AI, Ciocan C, Gulei D, Mehterov N, Atanasov AG, Dudea D, et al. Current Insights into Oral Cancer Epigenetics. Int J Mol Sci. 2018;19: pii: E670. 2. Warnakulasuriya S. Prognostic and predictive markers for oral squamous cell carcinoma: The importance of clinical, pathological and molecular markers. SJMMS. 2014;2:12-6. 3. Blatt S, Kruger M, Ziebart T, Sagheb K, Schiegnitz E, Goetze E, et al. Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: A review of the literature. J Cranio Maxill Surg. 2017;45:722-30. 4. Bremnes RM, Dønnem T, Al-Saad S, Al-Shibli K, Andersen S, Sirera R, et al. The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer. J Thorac Oncol. 2011;6:209-17. 5. Werb Z, Lu P. The Role of Stroma in Tumor Development. Cancer J. 2015;21:250-3. 6. Yoshida GJ, Azuma A, Miura Y, Orimo A. Activated Fibroblast Program Orchestrates Tumor Initiation and Progression; Molecular Mechanisms and the Associated Therapeutic Strategies. Int J Mol Sci. 2019;20:E2256. 7. Joshi PS, Patil J, Chougule M, Dudanakar M, Hongal BP. Evaluation of stromal myofibroblasts in epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study. Clin Cancer Investig J. 2016;5:441-6. 8. Bagul N, Ganjre A, Goryawala S, Kathariya R, Dusane S. Dynamic role of myofibroblasts in oral lesions. World J Clin Oncol. 2015;6:264. 9. Gabbiani G, Ryan G, Majno G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971;27:549-50. 10.Pinisetti S, Manyam R, Suresh B, Aparna V. Myofibroblasts in oral lesions: A review. Journal of oral and maxillofacial pathology : JOMFP. 2014;18:52-7. 11.Darby IA, Laverdet B, Bonté F, Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301-11. 12.Schurch W ST, Hinz B, Gabbiani G. Histology for Pathologists. Philadelphia: Lippincott-Williams and Wilkins Publishers; 2007. 13.Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR. Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res. 2002;8:2912-23. 14.Zhou J, Wang XH, Zhao YX, Chen C, Xu XY, Sun Q, et al. Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients. J Cancer. 2018;9:4635-41. 15.Rao S, Rao J, Bm J, Vk V. Mysterious Myofibroblast: A Cell with Diverse Origin and Multiple Functions. J Interdiscip Histopathol. 2016;5:12-7. 16.LeBleu VS, Kalluri R. A peek into cancer-associated fibroblasts: origins, functions and translational impact. Dis Model Mech. 2018;11:pii:dmm029447. 17.Tao L, Huang G, Song H, Chen Y, Chen L. Cancer associated fibroblasts: An essential role in the tumor microenvironment. Oncol Lett. 2017;14:2611-20. 18.Sewell-Loftin MK, Bayer SVH, Crist E, Hughes T, Joison SM, Longmore GD, et al. Cancer-associated fibroblasts support vascular growth through mechanical force. Sci Rep. 2017;7:12574. 19.Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141:52-67. 20.Smitha A, Rao K, Umadevi H, Smitha T, Sheethal H, Vidya M. Immunohistochemical study of alpha-smooth muscle actin expression in oral leukoplakia and oral squamous cell carcinoma. J Oral Maxillofac Pathol. 2019;23:59-64. 21.Kashima H, Noma K, Ohara T, Kato T, Katsura Y, Komoto S, et al. Cancer‐associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma. Int J Cancer. 2019;144:828-40. 22.Cho JG, Byeon HK, Oh KH, Baek SK, Kwon SY, Jung KY, et al. Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis. Eur Arch Otorhinolaryngol. 2018;275:2355-61. 23.National Society for Histotechnology (NSH). Guidelines for Hematoxylin and Eosin Staining. 2001. Available at: www.nsh.org. 24.Bratthauer GL. The avidin-biotin complex (ABC) method and other avidin-biotin binding methods. Methods Mol Biol. 2010;588:257-70. 25.Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, et al. Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with poor prognosis. Histopathology. 2007;51:849-53. 26.Vered M, Allon I, Buchner A, Dayan D. Stromal myofibroblasts accompany modifications in the epithelial phenotype of tongue dysplastic and malignant lesions. Cancer Microenviron. 2009;2:49-57. 27.Galdiero MR, Varricchi G, Loffredo S, Bellevicine C, Lansione T, Ferrara AL, et al. Potential involvement of neutrophils in human thyroid cancer. PloS one. 2018;13:e0199740. 28.Cadamuro M, Brivio S, Mertens J, Vismara M, Moncsek A, Milani C, et al. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. J Hepatol. 2019;70:700-9. 29.Rao SJ, Rao JBM, Rao PJ. Immunohistochemical analysis of stromal fibrocytes and myofibroblasts to envision the invasion and lymph node metastasis in oral squamous cell carcinoma. JOMFP. 2017;21:218-23. 30.Gupta K, Metgud R, Gupta J. Evaluation of stromal myofibroblasts in oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma--an immunohistochemical study. J Cancer Res Ther. 2015;11:893-8. 31.Jayaraj G, Sherlin HJ, Ramani P, Premkumar P, Natesan A. Stromal myofibroblasts in oral squamous cell Cancer. 2015;52:87-92.
32.Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, et al. Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol. 2008;44:509-17. 33.Etemad-Moghadam S, Khalili M, Tirgary F, Alaeddini M. Evaluation of myofibroblasts in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol Med. 2009;38:639-43. 34.Gandhi P, Prasad UC. Evaluation of myofibroblasts in oral submucous fibrosis and oral squamous cell carcinoma: The pathogenesis and correlation. Dent Res J (Isfahan). 2017;14:314-20. 35.Bhattacharjee K, Girish HC, Murgod S, Alshame AMJ, Shyamala K, Nayak VN. A Comparative Immunohistochemical Study of Presence and Distribution Pattern of Stromal Myofibroblast in Oral Dysplasia and in Different Grades of Oral Squamous Cell Carcinoma. J Int Soc Prev Community Dent. 2018;8:451-6. 36.Sridhara SU, Choudaha N, Kasetty S, Joshi PS, Kallianpur S, Tijare M. Stromal myofibroblasts in nonmetastatic and metastatic oral squamous cell carcinoma: An immunohistochemical study. JOMFP. 2013;17:190-4. 37.Seifi S, Shafaei S, Shafigh E, Sahabi SM, Ghasemi H. Myofibroblast stromal presence and distribution in squamous epithelial carcinomas, oral dysplasia and hyperkeratosis. APJCP. 2010;11:359-64. 38.Yeung TM, Buskens C, Wang LM, Mortensen NJ, Bodmer WF. Myofibroblast activation in colorectal cancer lymph node metastases. Br J Cancer. 2013;108:2106-15. 39.Itou RA, Uyama N, Hirota S, Kawada N, Wu S, Miyashita S, et al. Immunohistochemical characterization of cancer-associated fibroblasts at the primary sites and in the metastatic lymph nodes of human intrahepatic cholangiocarcinoma. Hum Pathol. 2019;83:77-89. 40. Parajuli H, Teh MT, Abrahamsen S, Christoffersen I, Neppelberg E, Lybak S, et al. Integrin α11 is overexpressed by tumor stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression. J Oral Pathol Med. 2017;46:267-75.
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