The present study aims to investigate the expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer of the uterine cervix, and their association with human papilloma virus (HPV) infection status. Uterine cervical biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 archival formalin-fixed, paraffin-embedded tissue specimens. Whole protein extracts were analyzed for the expression of 4EBP1 and eIF4E proteins using western blotting. In addition, distribution of 4EBP1 and eIF4E protein expression and 4EBP1 phosphorylation (P-4EBP1) were analyzed by immunohistochemistry in archival tissues and correlated with the degree of dysplasia. The presence of high-risk HPV (HR-HPV) types was assessed by polymerase chain reaction. Using western blot analysis, high expression levels of 4EBP1 and eIF4E were observed in all uterine cervical carcinomas, which significantly correlated with the degree of dysplasia. By immunohistochemistry, overexpression of 4EBP1 and eIF4E was detected in 20 of 21 (95%) and 17 of 21 (81%) samples, respectively, in patients with high-grade dysplasia and carcinomas, compared with 1 of 20 (5%) and 2 of 20 (10%) samples, respectively, in patients with low-grade lesions or normal histology. All 4EBP1-positive cases tested were also positive for P-4EBP1. Furthermore, overexpression of 4EBP1 and eIF4E significantly correlated with the presence of HR-HPV oncogenic types. The present study demonstrated that critical effectors of mTOR signaling, which control protein synthesis initiation, are overexpressed in cervical high-grade dysplasia and cancer, and their levels correlate with oncogenic HPV types. These findings may provide novel targets for investigational therapeutic approaches in patients with cancer of the uterine cervix.
The incidence of vaginal intraepithelial neoplasia (VaIN) is estimated at 0.2 to 0.3 cases per 100 000 women, consisting 1% of all intraepithelial neoplasia of the lower genital tract. 1-3 Studies have shown that VaIN constitutes a precursor lesion which may progress to vaginal carcinoma. 4,5 Potential risk factors for the development of VaIN involve promiscuity, early initiation of sexual intercourse, tobacco consumption and human papillomavirus (HPV) infection. Moreover, women with a history of cervical neoplasia or suffering from condylomata acuminata, are at increased risk of developing VaIN lesions compared with the general population. 6,7
The aim of the study was to determine the incidence and outcome of cervical intraepithelial neoplasia (CIN) in Greek young women. A retrospective analysis was conducted of women aged 16 - 20 years with a histological diagnosis of CIN during the years 1999-2005. Management was individualised for each case. The rates of regression, persistence and progression were measured. A total of 80 adolescents were identified. Some 54 patients (67.5%) had CIN1 and 26 (32.5%) had CIN2/3. Regression of the CIN1 lesions expressed as negative cytological or histological follow-up was observed in 74% and 93% of the patients at 12 and 24 months, respectively. The majority of adolescents (92%) with CIN2/3 underwent conisation and in 79% of them, histology of the specimen confirmed the initial diagnosis. CIN1 lesions will most likely regress over a 2-year period following diagnosis in women aged 16 - 20 years. Nevertheless, close monitoring is mandatory, as 10 - 15% of these lesions will either persist or progress to high-grade CIN. Management for adolescents with high-grade CIN lesions should be individualised according to a variety of parameters and adjusted to the patients' safety.
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