Sažetak
Uvod/Cilj. Prethodna istraživanja sugerišu da matriks-metaloproteinaze (MMP) imaju sposobnost da razgrađuju komponente vanćelijskog matriksa i imaju veliku ulogu u progresiji malignih tumora i nastanku metastaza. Cilj ove studije je bio da se ispita ekspresija MMP-2 i MMP-9 u tkivu skvamocelularnog karcinoma larinksa (SCKL) i da se proceni njihov klinički značaj. Metode. U prospektivnoj studiji, uzorci tumorskog tkiva 70 bolesnika sa SCKL (45 sa karcinomom glotisa i 25 sa karcinomom supraglotisa) i uzoraka tkiva sluznice larinksa 70 bolesnika sa hroničnim laringitisom bojeni su imunohistohemijski na MMP-2 i MMP-9. Ispitivana je povezanost između nivoa imunohistohemijske ekspresije MMP i kliničkih i histoloških karakteristika bolesnika sa SCKL u odnosu na bolesnike sa hroničnim laringitisom. Rezultati. Ekspresija MMP-2 i MMP-9 bila je značajno viša u tkivu glotičnog i supraglotičnog SCKL u odnosu na ekspresiju ispitivanih MMP u tkivu hronično inflamirane sluznice larinksa (p < 0,001 i p < 0,001, redom). Nađena je pozitivna korelacija između epitelne ekspresije MMP-2 i perineuralne invazije (r = 0,515; p < 0,008), limfovaskularne invazije (r = 0,559; p < 0,004) i pojave recidiva bolesti (r = 0,415; p = 0,039) kod supraglotičnog SCKL, kao i između ekspresije MMP-2 i pojave egzofitičnog tipa rasta tumora (r = 0,347; p = 0,020) kod glotičnog SCKL. Ekspresija MMP-9 u epitelu bila je povezana sa limfovaskularnom invazijom (r = 0,331; p = 0,026) i pojavom egzofitičnog tumorskog rasta (r = 0,474; p < 0,001) kod glotičnog SCKL. Zaključak. Endopeptidaze MMP-2 i MMP-9 mogu biti korišćene kao potencijalni biomarkeri za procenu progresije SCKL.
Ključne reči
glotis
imunohistohemija
larinks, neoplazme
laringitis
matriks metaloproteinaze
Reference
Smee R, Williams JR, Kotevski DP. Management of locally advanced T3-4 glottic laryngeal carcinomas. J Laryngol Otol 2018; 132(7): 642−50.
Tang D, Tao L, Zhou L, Zhang M, Wu X, Li X, et al. Retrospective analysis of 659 laryngeal squamous cell carcinoma patients treated with open laryngeal function-preserving operations. Acta Otolaryngol 2018; 138(11): 1043−50.
Whittaker M, Ayscough A. Matrix metalloproteinases and their inhibitors: current status and future challenges. Celltransmissions 2001; 17(1): 3−14.
Gou X, Chen H, Jin F, Wu W, Li Y, Long J, et al. Expressions of CD147, MMP-2 and MMP-9 in laryngeal carcinoma and its correlation with poor prognosis. Pathol Oncol Res 2014; 20(2): 475−81.
Rydlova M, Holubec L Jr, Ludvikova M Jr, Kalfert D, Franekova J, Povysil C, et al. Biological activity and clinical implications of the matrix metalloproteinases. Anticancer Res 2008; 28(2B): 1389−97.
Deschler DG, Moore MG, Smith RV. Quick Reference Guide to TNM Staging of Head and Neck Cancer and Neck Dissection Classification, 5th ed. Alexandria, VA: American Academy of Otolaryngology – Head and Neck Surgery Foundation; 2014.
Peschos D, Damala C, Stefanou D, Tsanou E, Assimakopoulos D, Vougiouklakis T, et al. Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions. Histol Histopathol 2006; 21(6): 603−8.
Uloza V, Liutkevicius V, Pangonyte D, Lesauskaite V. Characteristics of expression of matrix metalloproteinases (MMP-2 and MMP-9) in glottic squamous cell carcinoma and benign vocal fold lesions. Clin Exp Otorhinolaryngol 2015; 8(1): 57−64.
Lotfi A, Mohammadi G, Saniee L, Mousaviagdas M, Chavoshi H, Tavassoli A. Serum level of matrix metalloproteinase-2 and -9 in patients with laryngeal squamous cell carcinoma and clinical significance. Asian Pac J Cancer Prev 2015; 16(4): 1327−30.
Liu WW, Zeng ZY, Wu QL, Hou JH, Chen YY. Overexpression of MMP-2 in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis. Otolaryngol Head Neck Surg 2005; 132(3): 395−400.
Wael S, Manal S. Expression of nm23H1 and MMP2 in laryngeal carcinoma and its role in aggressiveness of the tumour and node metastasis. Egypt J Otolaryngol 2013; 29(2): 86−92.
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(9): 5301−10.
Sarioglu S, Ozer E, Kirimca F, Sis B, Pabuccuoglu U. Matrix metalloproteinase-2 expression in laryngeal preneoplastic and neoplastic lesions. Pathol Res Pract 2001; 197(7): 483−6.
Yuce I, Bayram A, Caglı S, Canoz O, Bayram S, Guney E. The role of CD44 and matrix metalloproteinase-9 expression in predicting neck metastasis of supraglottic laryngeal carcinoma. Am J Otolaryngol 2011; 32(2): 141−6.
Mallis A, Teymoortash A, Mastronikolis NS. MMP-2 expression in 102 patients with glottic laryngeal cancer. Eur Arch Otorhinolaryngol 2012; 269(2): 639−42.
Cao XL, Xu RJ, Zheng YY. Expression of type IV collagen, metalloproteinase-2, metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in laryngeal squamous cell carcinomas. Asian Pac J Cancer Prev 2011; 12(12): 3245−9.
Wittekindt C, Jovanovic N, Guntinas-Lichius O. Expression of matrix metalloproteinase-9 (MMP-9) and blood vessel density in laryngeal squamous cell carcinomas. Acta Otolaryngol 2011; 131(1): 101−6.
Colovic Z, Pesutić-Pisac V, Poljak NK, Racić G, Cikojević D, Kontić M. Expression of matrix metalloproteinase-9 in patients with squamous cell carcinoma of the larynx. Coll Antropol 2013; 37(1): 151−5.
Kalfert D, Ludvikova M, Topolcan O, Windrickova J, Malirova E, Pesta M, et al. Analysis of preoperatice serum levels of MMP-1, -2, -9 in patients with site-specific head and neck squamous cell cancer. Anticancer Res 2014; 34(12): 7431−41.
Li JZ, Gao W, Lei WB, Zhao J, Chan JY, Wei WI, et al. MicroRNA 744-3p promotes MMP-9 mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma. Oncotarget 2016; 7(36): 58218−23.
Popov TM, Stancheva G, Goranova TE, Rangachev J, Konov D, Todorov S, et al. Strong correlation between mRNA expression levels of HIF-2α, VEGFR1, VEGFR2 and MMP2 in laryngeal carcinoma. Pathol Oncol Res 2016; 22(4): 741−6.