350 rub
Journal Technologies of Living Systems №3 for 2012 г.
Article in number:
The expression of MMP-2 and MMP-9 in CIN and microinvasive cervical cancer as markers of progression and invasion
Keywords: CIN microinvasive cervical cancer MMP-2 MMP-9 progression markers invasion markers
Authors:
L.I. Korolenkova, E.V. Stepanova, V.D. Ermilova, A.Yu. Barishnikov, V.V. Bruzgin
Abstract:
Cervical cancerogenesis is associated with HR-HPV infection and may last for several years or decades. Three stages of CIN are the stages of cancerogenesis limited to epithelial layer and preceding invasive cervical cancer. Invasion correlates with poorer prognosis and increase risk of unfavorable outcome. CIN progression and invasion occurs not in every case, low-grade CIN may regress spontaneously. Prognosis of neoplasia course and progression to invasive disease is still challenging. Invasion is accompanied by expression of specific proteinases degrading components of basal membrane and extracellular matrix - including MMP-2 and MMP-9. The study of MMP-2 and MMP-9 expression pattern may help in diagnosis of close or existent latent invasion. The expression of MMP-2 and MMP-9 was assessed by immunohistochemical study in 81 CIN and microinvasive cancer tissue samples (CIN1 - 27, CIN2 - 25, CIN3 - 22, microinvasive cancer - 7 samples) and 10 cervical samples received in patients without CIN but with persistent HPV-infection. «Normal» samples as well as CIN1 and CIN2 samples showed no signs of MMP-2 and MMP-9 expression. Expression rate increased progressively along with the progression of CIN with significant up-regulation in microinvasive cancer when comparing to «normal» epithelium. Statistically significant difference was observed between expression rates of MMP-2 in CIN3 and CIN2 (p=0,03), microinvasive cancer and «normal» epithelium (p=0,004), CIN1 (p=0,002) and CIN2 (р<0,001). MMP-9 showed significant up-regulation when comparing microinvasive cancer and «normal» epithelium (p = 0,035) or CIN2 (p = 0,01). MMP-2 and MMP-9 expression rate increased progressively along with the progression of CIN and is associated with poorer prognosis, close or existent microinvasion. Absence of MMP-2 and MMP-9 is a specific feature of low-grade CIN - CIN1 and CIN2 with favorable prognosis. MMP-2 and MMP-9 co-expression may indicate on latent microinvasion with no evident morphological signs in conization samples. Immunohistochemical and immunocytochemical studies of MMP-2 and MMP-9 expression may constitute a part of testing system for individual CIN prognosis assessment, MMP-2 and MMP-9 are the promising markers for CIN progression and invasion.
Pages: 32-37
References
  1. Wright T.C. Jr., Massad L.S., Dunton C.J., Spitzer M., Wilkinson E.J. et al.2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ// J. Low Genit. Tract Dis. 2007. V. 11(4). P. 223 - 239.
  2. McCredie M.R., Sharples K.J., Paul C. et al.Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study // Lancet Oncol. 2008. V. 9. P. 425 - 434.
  3. Snijders P.J., Steenbergen R.D., Heideman D.A., Meijer C.J. HPV-mediated cervical carcinogenesis: concepts and clinical implications // J. Pathol. 2006. V. 208. P. 152 - 164.
  4. Song S.-H., Lee J.-K., Oh M.-J., Hur J.-Y., Park Y.-K., Saw H.-S. Risk factors for the progression or persistence of untreated mild dysplasia of the uterine cervix // Int. J. Gynecol. Cancer. 2006. V.16. P. 1608 - 1613.
  5. Tranbaloc P. Natural history of precursor lesions of cervical cancer // Gynecol. Obstet. Fertil. 2008. V. 36(6). P. 650 - 655.
  6. Al-Nafussi A.I., Monaghan H. Squamous carcinoma of the uterine cervix with CIN3-like growth pattern: an under-diagnosed lesion // Int. J. Gynecol. Cancer. 2000. V. 10. P. 95 - 99.
  7. Brummer O.,Böhmer G., Hollwitz B.et al.MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation--an immunohistochemical study //Gynecol. Oncol. 2002. V. 84(2). P.222 - 227.
  8. Malina R., Motoyama S., Hamana S., Maruo T. Laminin-5 gamma2 chain and matrix metalloproteinase-2 expression in the neoplastic changes of uterine cervical squamous epithelium // Kobe J. Med. Sci. 2004. V. 50(3 - 4). P. 123 - 130.
  9. Minami R., Tsunoda H., Iijima T. et al.Early acquisition of gelatinolytic activity in carcinogenesis of the uterine cervix // Mod. Pathol. 2003. V. 16(11). P. 1164 - 1170.
  10. Polette M., Nawrocki-Raby B., Gilles C. et al.Tumour invasion and matrix metalloproteinases // Crit. Rev. Oncol. Hematol. 2004. V. 49.  P. 179 - 186.
  11. Raza S.L., Cornelius L.A. Matrix metalloproteinases: pro- and anti-angiogenic activities // J. Investig. Dermatol. Symp. Proc. 2000. V. 5. P. 47 - 54.
  12. Zhai Y., Hotary K.B., Nan B. et al.Expression of membrane type 1 matrix metalloproteinase is associated with cervical carcinoma progression and invasion // Cancer Research. 2005.  V. 65(15). P. 6543 - 6550.
  13. Yu W., Liu J., Xiong X., Ai Y., Wang H. Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication // Pathol. Res. Pract. 2009.  V. 205(10). P.709 - 715.
  14. Davidson B., Goldberg I., Kopolovic J. et al. MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma - a clinicopathologic study sing immunohistochemistry and mRNA in situ hybridization // Gynecologic. Oncology. 1999. V. 73(3). P. 372 - 382.
  15. Talvensaari-Mattila A., Turpeenniemi-Hujanen T. Matrix metalloproteinase 9 in the uterine cervix during tumor progression // Int. J. Gynaecol. Obstet. 2006. V. 92(1). P. 83 - 84.