OBJECTIVETo compare the accuracy of transvaginal sonography and magnetic rezonance imaging (MRI) in determining the depth of myometrial invasion in proven cases of endometrial cancer.DESIGNA prospective study.SETTINGDepartment of Obstetrics and Gynecology, Department of Medical Genetics and Fetal Medicine, Department of Radiology, University Hospital, Olomouc.METHODSFifty five patients diagnosed as having FIGO stage I endometrial carcinoma were evaluated preoperatively by transvaginal ultrasound; 44 cases of the same group were also evaluated by magnetic resonance imaging (MRI). The degree of invasion evaluated by transvaginal sonography and by MRI was compared to the pathological specimens.RESULTSTransvaginal sonography was successful in evaluating myometrial invasion in 44 of 55 cases (accuracy 80%, sensitivity 80%, specificity 88%, positive predictive value 77%, negative predictive value 87%). Evaluation with MRI was accurate in 37 of 44 cases (accuracy 84%, sensitivity 84%, specificity 91%, positive predictive value 81%, negative predictive value 91%).CONCLUSIONAlthough MRI is superior to transvaginal sonography in evaluating myometrial invasion, it is expensive and time consuming, and would not be suitable as a screening test for depth of invasion. On the other hand, transvaginal sonography is relatively low-cost technique, which can be easily performed and repeated. However, it requires more operator experience than MRI in order to achieve high accuracy.

The aim of this study was to analyse whether DNA ploidy correlates with proliferative activity as measured by PCNA expression, presence of oncogenic human papillomaviruses (HPVs), histological grade, expression of antiapoptotic protein Bcl-2 and clinical outcome in a cohort of 57 preneoplastic and neoplastic lesions of the uterine cervix. The samples were analysed using computer image cytomorphometry of Feulgen stained sections, standard indirect immunohistochemistry and hybridisation of HPV DNA in situ. The ploidy data were found to be significantly different between low/high grade preneoplasia and invasive carcinoma. Significant positive relationships were also found between DNA content and proliferation of lesions, and DNA content and clinical behavior of the lesions. Nevertheless, no relationship between DNA ploidy and HPV/Bcl-2 status was established.

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death in a variety of tumors. The bcl-2 proto-oncogene is involved in the development of human follicular lymphomas and also in a number of solid tumors such as carcinomas of prostate, breast, lung and GIT. The present study was designed to analyze the role of Bcl-2 expression in cervical intraepithelial squamous neoplasias (CIN) and cervical invasive carcinomas. Special attention was given to the association of Bcl-2 expression with the grade of the lesion, proliferative activity (expression of nuclear antigen of proliferative cells - PCNA) and human papillomavirus (HPV) DNA positivity. We examined tissue samples obtained from 86 women with varying degrees of cervical disease. Bcl-2 and PCNA were investigated using immunohistochemical staining and detection of HPV DNA was performed by hybridization in situ. Increased Bcl-2 expression was observed in advanced degrees of dysplasia and in carcinomas. We found a strong association between the presence of Bcl-2 in pathological epithelium with both the degree of dysplasia and the proliferative activity. We also observed a significant correlation between the amount of Bcl-2 positive lymphocytes infiltrating the lesions and the degree of disease. We, therefore, suggest that Bcl-2 expression in these lymphocytes may influence the antiviral or antitumor immune response. On the other hand we did not detect any significant correlation between the Bcl-2 oncoprotein and the presence of HPV. These results indicate that Bcl-2 may play an important role in the development of cervical cancer.

Because the biological spectrum of human papillomavirus (HPV) genotypes present in cervical cancer lesions varies according to the geographical region studied, and because little genotype information is available for Central and Eastern European countries, we studied the endemic HPV-genotype spectrum in cervical samples collected from women visiting gynaecological departments of selected hospitals in the Czech Republic. In a series of 389 samples, 171 (44.0%) were positive for HPV DNA using a consensus-primer polymerase chain reaction (PCR). Genotyping of the HPV PCR products was done using dot-blot hybridisation with type-specific oligonucleotide probes and thermocycle DNA sequencing. Twenty-two different HPV types were detected, HPV-16 being the most prevalent type irrespective of severity of the lesions (55.0%). Multiple HPV types were found in 16.4% of our HPV-DNA-positive samples. The prevalence of HPV infection was 23.0% in women with normal findings and 59.4% in patients with cervical neoplasia, and increased significantly with the severity of the disease: 52.9% in low-grade lesions, 58.0% in high-grade lesions, and 73.5% in cervical carcinomas (P for trend < .00001). In the sera of 191 subjects, 89 with normal findings and 102 with different forms of cervical neoplasia, the prevalence of HPV-specific IgG antibodies was tested by an enzyme-linked immunosorbent assay (ELISA) using virus-like particles (VLPs) of HPV-16, -18, and -33. Antibodies were significantly more prevalent in HPV-DNA-positive than in HPV-DNA-negative women and there was no association with age. In agreement with the results of HPV genotyping, antibodies reactive with HPV-16 VLPs were the most frequent and, moreover, their prevalence increased with the cervical lesion severity. About half of the subjects with smears in which either HPV-16 or HPV-33 DNA had been detected possessed antibodies reactive with homotypic VLPs. With HPV-18-DNA-positive subjects, however, fewer than 25% displayed homotypic antibodies. In general, subjects older than 30 years of age had antibodies reactive to HPV-specific VLPs more often than subjects younger than 30 years of age. In women with benign findings, the seropositivity to HPV-16, -18, and -33 VLPs increased with age, whereas in women with cervical neoplasia the seropositivity decreased with age. J. Med. Virol. 58:378-386, 1999.

260 cases of women with epithelial neoplasias of the uterine cervix were studied: HPV infection was detected by DNA in situ hybridization and serology, simultaneously structure and intensity of stromal inflammatory reaction (SR) were evaluated (semiquantitatively) as well as standard clinical immunological parametres investigated by serology. Results proved the same character of SR in intraepithelial lesions and invasive carcinomas and the intensity of SR increasing in relation to the gravity of epithelial dysplasia. There was not found any significant difference in SR between cases with detected HPV infection and cases lacking it. Summarized immunological parametres were in limits of normal reference range.

We examined the cervical samples from 63 female patients with various grades of cervical intraepithelial neoplasia (CIN), invasive squamous cell carcinoma (INCA) or inflammation. All the women with the diagnosis of CIN were selected on the basis of cytological prediction of HPV infection (koilocytosis, dyskeratosis). The analysis of human papillomavirus (HPV) genome by DNA hybridization in situ was done in all cases. Simultaneously, the immunohistochemical expression of papillomavirus common antigen (PVCA) and proliferating cell nuclear antigen PCNA/cykline was determined. The results confirm the correlation between high risk HPV types 16, 18, 33 and higher grade of dysplasia (CIN) as well as higher proliferative activity. On the other hand, the detection of HPV DNA does not correlate with PVCA expression or with cytological/histological diagnosis of koilocytosis. This finding shows that common cytological or histological examinations may be unreliable and in particular the significance of koilocytosis must be reevaluated.

The DNA probes for HPV types 6, 11, 16, 18, 33 and 56 were prepared and biotinylated. They were used in hybridization in situ test for detection HPVs in the cells of 29 cervical samples with various grade of dysplasia and CIS. It was verified that DNA probes are suitable for HPV detection and that the grade of pathological changes is dependent on the presence of viral DNA. On the other hand, the pathological diagnosis of koilocytosis often do not reflect actual presence of HPV DNA in cell genome.