ORIGINAL ARTICLE
Prognostic significance of a panel of two biomarkers (E-cadherin and CD105) in laryngeal cancer
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1
Department of Otorhinolaryngology, Clinical Centre of Montenegro, Podgorica, Montenegro
2
Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
3
Department of Pathology, Clinical Centre of Montenegro, Podgorica, Montenegro
4
Department of Surgery, Clinical Centre of Montenegro, Podgorica, Montenegro
Submission date: 2023-01-15
Final revision date: 2023-08-22
Acceptance date: 2023-08-30
Publication date: 2024-01-17
Corresponding author
Elvir Zvrko
Elvir Zvrko
Department of Otorhinolaryngology
Clinical Centre of Montenegro
Podgorica, Montenegro
Pol J Pathol 2023;74(4):225-231
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TOPICS
ABSTRACT
This study aimed to evaluate the clinicopathologic significance of the combined immunohistochemical expression of the epithelial-mesenchymal transition marker E-cadherin and the angiogenesis marker CD105 in laryngeal squamous cell carcinoma and assess correlation of their expression.
Eighty-five patients who underwent complete resection as primary treatment were selected for this study. E-cadherin and CD105 expression levels were determined by immunohistochemistry. The receiver operating curve approach was applied to determine the cut-off value and separate patients with high and low expression of markers.
The high-risk group (“CD105 high” and “E-cadherin low” expression) showed statistically significant correlations with age less than 66 years (p = 0.039), advanced T-status (T3–4) (p = 0.046), aggressive TNM stage (stage III–IV) (p = 0.003) and locoregional recurrence of disease (p = 0.004). In the Kaplan-Meier analyses, the high-risk group had significantly worse prognoses than other risk groups (log-rank test 2 = 9.415, p = 0.024).
Spearman’s correlation coefficient analysis showed a nonsignificant negative correlation between the expression of E-cadherin and CD105 (rho = –0.073, p = 0.505). Simultaneous consideration of E-cadherin and CD105 is a simple panel of markers to determine aggressive tumour phenotype with a higher risk of disease recurrence in patients with laryngeal cancer.
REFERENCES (27)
1.
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-249.
2.
Bradford CR, Ferlito A, Devaney KO, et al. Prognostic factors in laryngeal squamous cell carcinoma. Laryngoscope Investig Otolaryngol 2020; 5: 74-81.
3.
Fassina A, Cappellesso R, Guzzardo V, et al. Epithelial- mesenchymal transition in malignant mesothelioma. Mod Pathol 2012; 25: 86-99.
4.
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119: 1420-1428.
5.
Marioni G, Nicolè L, Cappellesso R, et al. -Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma. Int J Biol Markers 2019; 34: 33-40.
6.
Loh CY, Chai JY, Tang TF, et al. The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges. Cells 2019; 8: 1118.
7.
Mitselou A, Galani V, Skoufi U, et al. Syndecan-1, epithelial-mesenchymal transition markers (E-cadherin/-catenin) and neoangiogenesis-related proteins (PCAM-1 and Endoglin) in colorectal cancer. Anticancer Res 2016; 36: 2271-2280.
8.
Cappellesso R, Marioni G, Crescenzi M, et al. The prognostic role of the epithelial-mesenchymal transition markers E-cadherin and Slug in laryngeal squamous cell carcinoma. Histopathology 2015; 67: 491-500.
9.
Greco A, De Virgilio A, Rizzo MI, et al. The prognostic role of E-cadherin and -catenin overexpression in laryngeal squamous cell carcinoma. Laryngoscope 2016; 126: E148-E155.
10.
Zhu GJ, Song PP, Zhou H, et al. Role of epithelial- mesenchymal transition markers E-cadherin, N-cadherin, -catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol Lett 2018; 15: 3472-3481.
11.
Zhang M, Li H, Han Y, et al. Clinicopathological significance of SOX4 and epithelial-mesenchymal transition markers in patients with laryngeal squamous cell carcinoma. Medicine (Baltimore) 2021; 100: e25028.
12.
Franz L, Nicolè L, Frigo AC, et al. Epithelial-to-mesenchymal transition and neoangiogenesis in laryngeal squamous cell carcinoma. Cancers (Basel) 2021; 13: 3339.
13.
Ribatti D. Epithelial-mesenchymal transition in morphogenesis, cancer progression and angiogenesis. Exp Cell Res 2017; 353: 1-5.
14.
Gurzu S, Kobori L, Fodor D, et al. Epithelial mesenchymal and endothelial mesenchymal transitions in hepatocellular carcinoma: A review. Biomed Res Int 2019; 2019: 2962580.
15.
Jin W. Role of JAK/STAT3 signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial-mesenchymal transition. Cells 2020; 9: 217.
16.
Saad RS, Liu YL, Nathan G, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 2004; 17: 197-203.
17.
Zvrko E, Mikic A, Vuckovic L, et al. Prognostic relevance of CD105-assessed microvessel density in laryngeal carcinoma. Otolaryngol Head Neck Surg 2009; 141: 478-483.
18.
Lovato A, Marioni G, Manzato E, et al. Elderly patients at higher risk of laryngeal carcinoma recurrence could be identified by a panel of two biomarkers (nm23-H1 and CD105) and pN+ status. Eur Arch Otorhinolaryngol 2015; 272: 3417-3424.
19.
Marioni G, Franz L, Ottaviano G, et al. Prognostic significance of CD105- and CD31-assessed microvessel density in paired biopsies and surgical samples of laryngeal carcinoma. Cancers (Basel) 2020; 12: 2059.
20.
Hu J, Guan W, Yan L, et al. Cancer stem cell marker endoglin (CD105) induces epithelial mesenchymal transition (EMT) but not metastasis in clear cell renal cell carcinoma. Stem Cells Int 2019; 2019: 9060152.
21.
Head and Neck Cancer Study Group (HNCSG), Monden N, Asakage T, Kiyota N, et al. A review of head and neck cancer staging system in the TNM classification of malignant tumors (eighth edition). Jpn J Clin Oncol 2019; 49: 589-595.
22.
Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis- correlation in invasive breast carcinoma. N Engl J Med 1991; 324: 1-8.
23.
Rodrigo JP, Dominguez F, Suárez V, et al. Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007; 133: 145-150.
24.
Paksoy M, Hardal U, Caglar C. Expression of cathepsin D and E-cadherin in primary laryngeal cancers correlation with neck lymph node involvement. J Cancer Res Clin Oncol 2011; 137: 1371-1377.
25.
Zhang J, Sang X, Zhang R, et al. CD105 expression is associated with invasive capacity in ovarian cancer and promotes invasiveness by inhibiting NDRG1 and regulating the epithelial-mesenchymal transition. Am J Transl Res 2021; 13: 12461-12479.
26.
Kim SW, Roh J, Park CS. Immunohistochemistry for pathologists: Protocols, Pitfalls, and Tips. J Pathol Transl Med 2016; 50: 411-418.
27.
Søreide K. Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research. J Clin Pathol 2009; 62: 1-5.