Prognostički značaj imunohistohemijskih parametara i histomorfološkog skora u proceni težine displazije epitela grlića materice

Abstract

Cilj:Karcinom grlića je treći po uĉestalosti u svetu meĊu malignim bolestima. Displazije epitela grlića predstavljaju niz prekursorskih lezija karcinoma grlića.Najznacajniji faktor rizika za displaziju epitela grlića jeste infekcija humanim papiloma virusima.Cilj ove disertacije je bio da se utvrdi dijagnostiĉki znaĉaj imunohistohemijskih metoda markerima p16, p63, ciklin d1 i survivin u epitelnim displazijama grlića,morfometrijske nalize i histomorfološkog skora. Metodologija:Retrospektivnom studijom je bilo obuhvaćeno 100 pacijentkinja pregledanih na Ginekološkom odeljenju Vojnomedicinske akademije u trogodišnjem periodu.Kriterijumi za ulazak u studiju su: primarna, ranije netretirana lezija, kolposkopski nalaz koji upućuje na prisustvo premaligne lezije grlića: uĉinjen citološki test epitela grlića po metodi Papanikolau koji je interpretiran po Bethesda kriterijumu sa nalazom displazije lakog stepena (low-grade squamous intraepithelial lesion,LSIL), displazije teškog stepena (high-grade sqamous intraepithelial lesion,HSIL), atipiĉnih ćelija neodreĊenog znaĉaja (atypical squamous cells of undeterminated significance,ASCUS);uĉinjena tipizacija humanih papiloma virusa reakcijom lanĉane polimerizacije sa dokaznim prisustvom virusa tipa 16,18,31,33 kod svih zena. Ovoj grupi pacijentkinja je uradjena biopsija, imunohistohemijske i morfometrijske analize bioptiranog tkiva. Primenjena su imunohistohemijska bojenja p16, p63, ciklin d1 i survivin. Analiza imunohistohemijskih reakcija je vršena svetlosnim mikroskopom u zonama displazije. Od 100 zena koje su ušle u studiju, kod kojih je prvom biopsijom dokazano prisustvo displazije (HSIL, LSIL), kod 48 zena je ucinjena ponovna biopsija u perodu do sedam meseci, na osnovu istih dijagnostickih kriterijuma kao za prvu biopsiju, gde su primenjivane sve metode istraživanja koje su korišćene u prvoj biopsiji. Kontrolnu grupu su ĉinile 12 žena,koje su se javile na kontrolni pregled bez displazije i bez verifikovane infekcije grlića materice visokoriziĉnim HPV virusima, zbog mioma, na materijalu dobijenom nakon histerektomije...

Aim:Cervical cancer is the third most common cancer in the world.Cervical dysplasia, such as minor and severe dysplasia, is a group of precursor lesion of the squamous cell carcinoma. The most important etiologic risk factors for dysplasia are infection with the human papilloma virus (HPV).The aim of this study was to determine the relevance of correlation between epithelial p16,p63,ciklin d1 and survivin expression and the degree of human papilloma virus (HPV)- induced cervical epithelial dysplasia, as well as, to establish the significance of morphometric analysis of nuclear area and histomorphologic score in assessment of cervical dysplasia degrees Methodology: This retrospective study included 100 patients examined at the Department of Gynaecology of the Military Medical Academy in the period from three years.Criteria for inclusion into the study were primary, previously untreated lesions, colposcopic findings that suggest the presence of premalignant lesions of the cervix; findings from Papanikolaou cytological test, interpreted by the Bethesda criteria with the findings of LSIL, HSIL, ASCUS. HPV typisation was done by PCR with evidence of viruses type 16, 18, 31 and 33 in all women. After the bipsy of the cervical mucosa, we performed pathohistological analysis by hematoxilineosin staining, immunohistochemical analysis for p16,p63,ciklin d1 and survivin and morphometric analysis of cervical epithelium. After the first biopsy, during next seven months in group of 48 patients with dysplasias, according the same criteria for inclusion, we performed rebiopsy and uniform examination . The control group consisted of 12 women without dysplasia and without verified infection of cervical high-risk HPV, with pathological diagnosis of leiomyoma in material obtained after the hysterectomy.Criteria for exclusion from the study was previously diagnosed and treated dysplasia or squamous cell carcinoma...