Journal of Carcinogenesis & Mutagenesis

Abstract

Cervical Intraepithelial Neoplasia-Predictive Molecular Growth Factors in Natural History

Robert Jach, Bartlomiej Galarowicz, Klaudia Stangiel-Wójcikiewicz, Tomasz Banas, Joanna Streb, Artur Ludwin, Inga Ludwin and Grzegorz Dyduch

There is considerable controversy regarding the possible over-treatment of patients with mild Cervical Intraepithelial Neoplasia (CIN), with lesions being often excised or ablated. Thus, identifying the markers of potentially malignant lesions would be of a great prognostic value. In the current study, we hypothesized that using colposcopic, cytological and histological findings together with assessing the expression of molecular growth factors can predict CIN outcome. The study group consisted of 285 women between 19 and 81 years of age (median age, 37,8 years). The follow up were 60 months and considered 138 women: 50 women with Subclinical Papillomavirus Infection (SPI), 50 women with CIN1 and 38 women with CIN2.  All patients underwent cytology, colposcopy, and sampling for subsequent testing for HPV. In cases in which colposcopy suggested the presence of suspicious lesions, biopsy specimens were taken. HPV DNA was genotyped for HPV types 16, 18, 31, 33, and 45 by multiplex PCR. Transcripts of HR HPV types 16, 18, 31, 33, and 45 were detected by the NucliSens EasyQ HPV assay. The VEGF expression was analyzed with immunohistochemistry, RNA extraction, cDNA synthesis and RT-PCR analysis and Western blot.  We found that so called lymphangiogenetic switch (over expression of VEGF C and VEGFR-2) appears already in CIN 2, which is a rare observation, Persistent HPV HR infection is not only a trigger but also a maintenance factor in the cervical carcinogenesis. CIN2/3 and cervical cancer is in high percentage associated with the presence of HR DNA HPV as well as E6/E7 DNA mRNA. In CIN2/3 and cervical cancer VEGF and its receptor expression correlate with the stage of cervical carcinogenesis. Progression of cervical intraepithelial neoplasia occurs when co expression of all: HR DNA HPV, E6/E7 HR HPV mRNA and VEGF is present.