A Pilot Study on Immunohistochemical Expressions of NF-ĸB, Cyclin-D1, VEGF, and Cox-2 in Advanced Stage Laryngeal Carcinoma
Abstract
BACKGROUND: Progression of laryngeal carcinoma can be classified with the clinical staging, however there are different patterns of progressions observed in the patient with the same clinical stage which also affects their prognoses. Therefore biomarkers should be used. Nuclear factor (NF)-ĸB, Cyclin-D1, vascular endothelial growth factor (VEGF), cyclooxygenase (Cox)-2 have been reported for laryngeal carcinoma. However, it is still unclear how these markers are expressed and correlated in advanced stage laryngeal carcinoma. Therefore current study was conducted to investigate the expressions of NF-ĸB, Cyclin-D1, VEGF and Cox-2 and their correlations in advanced stage laryngeal carcinoma.
METHODS: Subjects were recruited and laryngeal biopsies were collected, fixed in formalin and prepared for immunohistochemistry. The immunohistochemistry was performed using mouse monoclonal anti-NF-kB p65, anti-Cyclin-D12 anti-VEGF, and anti-Cox-2 antibodies. The immunohistochemistry results were documented and measured using ImmunoRatio. Pearson or Spearman correlation test was used based on the results of Shapiro-Wilk test of normality. A p-value of less than 0.05 is considered statistically significant.
RESULTS: Twelve male subjects were included in this study. Expressions of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 were clearly observed. Mean of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 IHC expression levels measured with ImmunoRatio were 57.50±20.06%, 45.00±24.31%, 43.33±17.23% and 40.42±16.98%, respectively. There was significant correlation between the expressions of VEGF dan Cox-2 (p=0.031, r=0.622).
CONCLUSION: Since correlation between the VEGF and Cox-2 expressions was statistically significant, VEGF and Cox-2 might have important roles in the growth, invasion and metastasis of laryngeal carcinoma.
KEYWORDS: advanced stage laryngeal carcinoma, immunohistochemistry, NF-ĸB, Cyclin-D1, VEGF, Cox-2
Full Text:
PDFReferences
Kontos CK. Molecular biomarkers of prognosis in laryngeal squamous cell carcinoma. OA Cancer. 2013; 1: 12, CrossRef.
Putri S, Dewi Y, Dewayani B. Risk factors of laryngeal carcinoma in Otorhinolaryngology-Head and Neck Division of Dr. Hasan Sadikin Hospital Bandung. J Med Health. 2018; 2: 1007, CrossRef.
Akdeniz O, Akduman D, Haksever M, Ozkarakas H, Muezzinoglu B. Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, MMP-9 and E-Cadherin. Asian Pac J Cancer Prev. 2013; 14: 5301-10, CrossRef.
Park M, Hong J. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells. 2016; 5: 15, CrossRef.
Sandra F, Kukita T, Tang QY, Iijima T. Caffeic acid inhibits NFkappaB activation of osteoclastogenesis signaling pathway. Indones Biomed J. 2011; 3: 216-22, CrossRef.
Hendarmin L, Kawano S, Yoshiga D, Sandra F, Mitsuyasu T, Nakao Y, et al. An anti-apoptotic role of NF-κB in TNFα-induced apoptosis in an ameloblastoma cell line. Oral Sci Int. 2008; 5: 96-103, CrossRef.
Rahaju P, Kintono R, Wahyudiono A, Satria A, Sandra F. Immunohistochemical expression of EGFR, NF-kB and Cyclin D1 in sinonasal inverted papilloma and squamous cell carcinoma. Indones Biomed J. 2020; 12: 239-44, CrossRef.
John RR, Malathi N, Ravindran C, Anandan S. Mini review: Multifaceted role played by cyclin D1 in tumor behavior. Indian J Dent Res. 2017; 28: 187-92, CrossRef.
Lukito B, Suriapranata I, Pendrianto P, Sulaiman A, Yusuf I, Suhadi FXB, et al. Vascular endothelial growth factor level as a predictor of hepatocellular carcinoma in liver cirrhosis patients. Indones Biomed J. 2014; 6: 167-74, CrossRef.
Akdeniz O, Akduman D, Haksever M, Ozkarakas H, Muezzinoglu B. Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, MMP-9 and E-Cadherin. Asian Pac J Cancer Prev. 2013; 14: 5301-10, CrossRef.
Hoeben A, Landuyt B, Highley M, Wildiers H, Van Oosterom A, De Bruijn E. Vascular endothelial growth factor and angiogenesis. Pharmacological Rev. 2004; 56: 549-80, CrossRef.
Hashemi G, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: A review. J Cell Physiol. 2018; 234: 5683-99, CrossRef.
Iype E, Balakrishna R, Subhadradevi L, Vinoda Thulaseedharan J, Singh R, Jayasree K. Cyclooxygenase-2 expression in squamous cell carcinoma of larynx: association with clinico-pathological factors and treatment outcomes. Int J Otorhinolaryngol Head Neck Surg. 2021; 4: 970-6, CrossRef.
Yang B, Jia L, Guo Q, Ren H, Hu Y, Xie T. Clinicopathological and prognostic significance of cyclooxygenase-2 expression in head and neck cancer: a meta-analysis. Oncotarget. 2016; 7: 47265-77, CrossRef.
Edge S, Byrd D, Compton C, Fritz A, Greene F, Trotti A. AJCC Cancer Staging Manual, Larynx Staging Form. 8th ed. New York: Springer; 2017, NLMID.
Abbas NF, El-Sharkawy SL, Abbas EA, El-Shaer MAM. Immunohistochemical study of p53 and angiogenesis in benign and preneoplastic oral lesions and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2007; 103: 385-90, CrossRef.
Dong Y, Sui L, Sugimoto K, Tai Y, Tokuda M. Cyclin D1‐CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas. Int J Cancer. 2001; 95: 209-15, CrossRef.
Chen Z, Yan B, Van Waes C. Role of the NF-kB transcriptome and proteome as biomarkers in human head and neck squamous cell carcinomas. Biomarker Med. 2008; 2: 409-26, CrossRef.
Gunantara I, Dewi I, Artha I. Ekspresi vascular endothelial growth factor berhubungan positif dengan kedalaman invasi pada adenokarsinoma kolorektal. Majalah Patologi Indones. 2019; 28: 44-9, article.
Guangli C, Yingpeng L, Jianting W, Linghui L, Pei C, Juan D, et al. Expression of vascular endothelial growth factor and cyclooxygenase-2 in laryngeal squamous cell carcinoma and its significance. J Huazhong Univ Sci Technol. 2006; 26: 105-7, CrossRef.
Yuan A, Yu C, Shun C, Luh K, Kuo S, Lee YC, et al. Total cyclooxygenase‐2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non‐small cell lung cancer patients. Int J Cancer. 2005; 115: 545-55, CrossRef.
DOI: https://doi.org/10.18585/inabj.v13i4.1580
Copyright (c) 2021 The Prodia Education and Research Institute

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:





The Prodia Education and Research Institute