Vol 61, No 3 (2023)
Original paper
Published online: 2023-10-03

open access

Page views 462
Article views/downloads 212
Get Citation

Connect on Social Media

Connect on Social Media

Expression of CD105 but not of E-cadherin is associated with malignancy recurrence and disease-free interval in laryngeal cancer in men

Elvir Zvrko12, Ljiljana Vuckovic23
Pubmed: 37787034
Folia Histochem Cytobiol 2023;61(3):183-192.

Abstract

Introduction. In this study we analyzed CD105 (endoglin) and E-cadherin expression in laryngeal squamous cell carcinoma (LSCC) to evaluate their clinicopathologic significance.

Material and methods. Expression of CD105 and E-cadherin was examined immunohistochemically using paraffin-embedded archival tissues of 72 (35 glottic and 37 supraglottic) previously untreated LSCC male patients. The mean value of the positively-stained microvessels for CD105 counted in four hot spots for each case was used as the final intratumoralmicrovessel density (MVD). A staining score of E-cadherin was calculated based on the percentage of cells stained (0–100%).

Results. MVD was significantly higher in patients with advanced TNM stage (P = 0.004) and younger than 65 (P = 0.008). Nodal metastases were more frequent in the cases with low E-cadherin expression (P = 0.000). Tumor recurrence was associated with advanced TNM stage (P = 0.035) and high MVD (P = 0.002). A high MVD was an independent predictor of malignancy recurrence (P = 0.021). The log-rank test showed a significant difference in the disease-free interval in patients stratified according to the MVD value (P = 0.016). Spearman’s rank correlation test did not show a significant correlation between E-cadherin and CD105 expression.

Conclusions. CD105-assessed MVD and expression of E-cadherin are promising prognostic factors for the outcome of patients with LSCC. Increased expression of CD105 could help predict patients with an increased risk of developing loco-regional recurrence after surgical treatment. Decreased E-cadherin expression is a potential predictor of lymph node metastases.

Article available in PDF format

View PDF Download PDF file

References

  1. Nocini R, Molteni G, Mattiuzzi C, et al. Updates on larynx cancer epidemiology. Chin J Cancer Res. 2020; 32(1): 18–25.
  2. Bradford CR, Ferlito A, Devaney KO, et al. Prognostic factors in laryngeal squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2020; 5(1): 74–81.
  3. Prognostic factor definition. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/prognostic-factor (6.01.2023).
  4. Johansen LV, Grau C, Overgaard J. Laryngeal carcinoma — multivariate analysis of prognostic factors in 1252 consecutive patients treated with primary radiotherapy. Acta Oncol. 2003; 42(7): 771–778.
  5. Chen AY, Halpern M. Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg. 2007; 133(12): 1270–1276.
  6. Bøje CR. Impact of comorbidity on treatment outcome in head and neck squamous cell carcinoma — a systematic review. Radiother Oncol. 2014; 110(1): 81–90.
  7. Li ZQ, Zou L, Liu TR, et al. Prognostic value of body mass index before treatment for laryngeal squamous cell carcinoma. Cancer Biol Med. 2015; 12(4): 394–400.
  8. Bonner J, Giralt J, Harari P, et al. Cetuximab and radiotherapy in laryngeal preservation for cancers of the larynx and hypopharynx: a secondary analysis of a randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2016; 142(9): 842–849.
  9. Atef A, El-Rashidy MA, Elzayat S, et al. The prognostic value of sex hormone receptors expression in laryngeal carcinoma. Tissue Cell. 2019; 57: 84–89.
  10. Ahmadi N, Ahmadi N, Chan MV, et al. Laryngeal squamous cell carcinoma survival in the context of human papillomavirus: a systematic review and meta-analysis. Cureus. 2018; 10(2): e2234.
  11. Coca-Pelaz A, Rodrigo JP, Suárez C, et al. The risk of second primary tumors in head and neck cancer: a systematic review. Head Neck. 2020; 42(3): 456–466.
  12. Franz L, Nicolè L, Frigo AC, et al. Epithelial-to-mesenchymal transition and neoangiogenesis in laryngeal squamous cell carcinoma. Cancers (Basel). 2021; 13(13).
  13. Litwiniuk-Kosmala M, Makuszewska M, Czesak M. Endoglin in head and neck neoplasms. Front Med (Lausanne). 2023; 10: 1115212.
  14. Mineo TC, Ambrogi V, Baldi A, et al. Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol. 2004; 57(6): 591–597.
  15. Nagatsuka H, Hibi K, Gunduz M, et al. Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas. J Oral Pathol Med. 2005; 34(2): 70–76.
  16. Li SL, Gao DL, Zhao ZH, et al. Correlation of matrix metalloproteinase suppressor genes RECK, VEGF, and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma. World J Gastroenterol. 2007; 13(45): 6076–6081.
  17. Sánchez-Elsner T, Botella LM, Velasco B, et al. Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J Biol Chem. 2002; 277(46): 43799–43808.
  18. Miyata Y, Sagara Y, Watanabe Si, et al. CD105 is a more appropriate marker for evaluating angiogenesis in urothelial cancer of the upper urinary tract than CD31 or CD34. Virchows Arch. 2013; 463(5): 673–679.
  19. Marioni G, Giacomelli L, D’Alessandro E, et al. Laryngeal carcinoma recurrence rate and disease-free interval are related to CD105 expression but not to vascular endothelial growth factor 2 (Flk-1/Kdr) expression. Anticancer Res. 2008; 28(1B): 551–557.
  20. Zvrko E, Mikic A, Vuckovic L. CD105 expression as a measure of microvessel density in supraglottic laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2009; 266(12): 1971–1976.
  21. Zvrko E, Mikic A, Vuckovic L, et al. Prognostic relevance of CD105-assessed microvessel density in laryngeal carcinoma. Otolaryngol Head Neck Surg. 2009; 141(4): 478–483.
  22. 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(11): 3417–3424.
  23. 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(8).
  24. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6): 1420–1428.
  25. Loh CY, Chai JYi, Tang TF, et al. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells. 2019; 8(10).
  26. Kaszak I, Witkowska-Piłaszewicz O, Niewiadomska Z, et al. Role of cadherins in cancer — a review. Int J Mol Sci. 2020; 21(20).
  27. Piprek RP, Kloc M, Mizia P, et al. The central role of cadherins in gonad development, reproduction, and fertility. Int J Mol Sci. 2020; 21(21).
  28. Punovuori K, Malaguti M, Lowell S. Cadherins in early neural development. Cell Mol Life Sci. 2021; 78(9): 4435–4450.
  29. Marioni G, Nicolè L, Cappellesso R, et al. β-Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma. Int J Biol Markers. 2019; 34(1): 33–40.
  30. Zvrko E, Mikić A, Jancić S. Relationship of E-cadherin with cervical lymph node metastasis in laryngeal cancer. Coll Antropol. 2012; 36 Suppl 2: 119–124.
  31. Zhu GJ, Song PP, Zhou H, et al. Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, β-catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol Lett. 2018; 15(3): 3472–3481.
  32. 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(12): e25028–1175.
  33. 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(9): 1371–1377.
  34. Yüce İ, Çağlı S, Canöz Ö, et al. Predictive value of E-cadherin and Ep-CAM in cervical lymph node metastasis of supraglottic larynx carcinoma. Am J Otolaryngol. 2015; 36(6): 736–740.
  35. Barutçu O, Kara M, Muratlı A, et al. Clinical significance of Ki-67, c-erbB-2 and E-cadherin expressions in open partial laryngectomy patients. Kulak Burun Bogaz Ihtis Derg. 2016; 26(5): 283–292.
  36. Kejner AE, Li H, Li EY, et al. Treatment modality and outcomes in larynx cancer patients: A sex-based evaluation. Head Neck. 2019; 41(11): 3764–3774.
  37. Saini AT, Genden EM, Megwalu UC. Sociodemographic disparities in choice of therapy and survival in advanced laryngeal cancer. Am J Otolaryngol. 2016; 37(2): 65–69.
  38. Fakhry C, Westra WH, Wang SJ, et al. The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer. Cancer. 2017; 123(9): 1566–1575.
  39. Monden N, Asakage T, Kiyota N, et al. Head and Neck Cancer Study Group (HNCSG). A review of head and neck cancer staging system in the TNM classification of malignant tumors (eighth edition). Jpn J Clin Oncol. 2019; 49(7): 589–595.
  40. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma. N Engl J Med. 1991; 324(1): 1–8.
  41. 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(2): 197–203.
  42. Kumar S, Ghellal A, Li C, et al. Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res. 1999; 59(4): 856–861.
  43. Yagasaki H, Kawata N, Takimoto Y, et al. Histopathological analysis of angiogenic factors in renal cell carcinoma. Int J Urol. 2003; 10(4): 220–227.
  44. Martone T, Rosso P, Albera R, et al. Prognostic relevance of CD105+ microvessel density in HNSCC patient outcome. Oral Oncol. 2005; 41(2): 147–155.
  45. Kyzas PA, Agnantis NJ, Stefanou D. Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma. Virchows Arch. 2006; 448(6): 768–775.
  46. Gu X, Xu Y, Wu He, et al. [Relationship between CD105 and angiogenesis and biological behaviors in squamous carcinoma of larynx]. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006; 20(3): 125–128.
  47. Chen HC, Chu RY, Hsu PN, et al. Loss of E-cadherin expression correlates with poor differentiation and invasion into adjacent organs in gastric adenocarcinomas. Cancer Lett. 2003; 201(1): 97–106.
  48. Köksal IT, Ozcan F, Kiliçaslan I, et al. Expression of E-cadherin in prostate cancer in formalin-fixed, paraffin-embedded tissues: correlation with pathological features. Pathology. 2002; 34(3): 233–238.
  49. Kanazawa T, Watanabe T, Kazama S, et al. Poorly differentiated adenocarcinoma and mucinous carcinoma of the colon and rectum show higher rates of loss of heterozygosity and loss of E-cadherin expression due to methylation of promoter region. Int J Cancer. 2002; 102(3): 225–229.
  50. Sarrió D, Pérez-Mies B, Hardisson D, et al. Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. Oncogene. 2004; 23(19): 3272–3283.
  51. Franchi A, Gallo O, Boddi V, et al. Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination. Clin Cancer Res. 1996; 2(10): 1801–1808.
  52. Rodrigo JP, Domínguez F, Alvarez C, et al. Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features. Eur J Cancer. 2002; 38(8): 1059–1064.
  53. Akdeniz O, Akduman D, Haksever M, et al. 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(9): 5301–5310.
  54. Ahmed RA, Shawky AEA, Hamed RH. Prognostic significance of cyclin D1 and E-cadherin expression in laryngeal squamous cell carcinoma. Pathol Oncol Res. 2014; 20(3): 625–633.
  55. Andrews NA, Jones AS, Helliwell TR, et al. Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. Br J Cancer. 1997; 75(10): 1474–1480.
  56. Takes RP, Baatenburg de Jong RJ, Schuuring E, et al. Markers for assessment of nodal metastasis in laryngeal carcinoma. Arch Otolaryngol Head Neck Surg. 1997; 123(4): 412–419.
  57. 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(4): 491–500.
  58. Li Q, Zhang B, Peng P. [Relevance of Endoglin (CD105) VEGF and p53 with invasion metastasis and prognosis of laryngeal carcinoma]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2007; 21(24): 1114–1117.
  59. Marioni G, Ottaviano G, Giacomelli L, et al. CD105-assessed micro-vessel density is associated with malignancy recurrence in laryngeal squamous cell carcinoma. Eur J Surg Oncol. 2006; 32(10): 1149–1153.
  60. Gordon MS, Robert F, Matei D, et al. An open-label phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) with bevacizumab in patients with advanced cancer. Clin Cancer Res. 2014; 20(23): 5918–5926.
  61. Dorff TB, Longmate JA, Pal SK, et al. Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. Cancer. 2017; 123(23): 4566–4573.
  62. Galanis E, Anderson SK, Twohy E, et al. Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance). Neurooncol Adv. 2022; 4(1): vdac041.



Folia Histochemica et Cytobiologica