Correlation between cyclin B1 immunostaining in cervical biopsies and HPV detection by PCR.

In recent years, experimental data on the roles of viruses and cyclin B1 in G2/M arrest has accumulated. The aim of our study was to immunohistochemically examine a series of cervical squamous intraepithelial lesions for the presence of cyclin B1 and test for a possible correlation with morphologic findings or human papillomavirus (HPV) types detected by polymerase chain reaction. One hundred and three biopsies and/or conization specimens were examined, including high-grade lesions (25), low-grade lesions (52), biopsies showing nondiagnostic atypia (15), and biopsies without histopathologic alterations (11). Three patterns of immunopositivity were recognized, according to the level of epithelium exhibiting positively stained cells. Immunoreactivity for cyclin B1 above the basal/parabasal cells correlated with HPV presence. Cyclin B1-stained cells may represent "prekoilocytes," whose eventual progression to koilocytes would depend on several parameters related to the intricacies of HPV infection. In cases of nondiagnostic atypia immunoreactivity, cyclin B1 could be considered as a surrogate test.

Quantitative determination of human telomerase reverse transcriptase messenger RNA expression in premalignant cervical lesions and correlation with human papillomavirus load.

Expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA) and human papillomavirus (HPV)-16 load were quantified using real-time polymerase chain reaction and correlated with cytological findings and the presence of HPV infection in cervical specimens. Human telomerase reverse transcriptase mRNA expression was evaluated in 15 (20.5%) of 73 specimens of atypical squamous epithelial cells of undetermined significance, in 62 (39.7%) of 156 low-grade squamous intraepithelial lesions (LGSILs), in 49 (96%) of 51 high-grade squamous intraepithelial lesions (HGSILs), and in 9 (20%) of 45 normal samples, whereas viral load was quantified in 52 (89.6%) of 58 samples infected with HPV-16. The mean levels of hTERT mRNA expression were 0.11 in normal tissue, 0.23 in atypical squamous epithelial cells of undetermined significance, 0.75 in LGSILs, and 2.5 in HGSILs. Thus, a significant increase in hTERT mRNA expression was observed with increasing degrees of cervical dysplasia. The HPV-16 load was significantly higher in samples of HGSIL than in those of LGSILs (P < .001). A significant correlation was observed between viral load and quantitative hTERT mRNA expression (r = 0.65; P < .05). Quantitative hTERT mRNA assessment showed 96% sensitivity and 100% negative predictive value for high-grade dysplasia, whereas the specificity and positive predictive value were 72% and 36.2%, respectively. It is suggested that quantitative hTERT has a very high sensitivity and negative predictive value, whereas the observed specificity was moderate, indicating that it cannot be used as a diagnostic marker but may be an adjunct in the management of women with high-grade cervical dysplasia. However, the final diagnosis must rely on the inclusion of clinical evaluation and additional assessment data.

Evidence of differential control of FSH and LH responses to GnRH by ovarian steroids in the luteal phase of the cycle.

BACKGROUND: It is known that during the follicular phase of the cycle, estradiol sensitizes the pituitary to GnRH. The aim of this study was to determine the role of ovarian steroids in the control of GnRH-induced gonadotrophin secretion in the luteal phase of the cycle. METHODS: Eighteen normally cycling women were studied during the week following bilateral ovariectomy plus hysterectomy performed in early to mid-luteal phase. Six of the women received no hormonal treatment post-operatively (group 1, control), six received estradiol through skin patches (group 2) and the remaining six received estradiol plus progesterone (group 3). In all women the response at 30 min of LH (deltadeltaLH) and FSH (deltadeltaFSH) to GnRH (10 microg i.v.) was investigated on a daily basis. RESULTS: In group 1, serum FSH, LH and deltadeltaFSH values increased progressively following ovariectomy, while in groups 2 and 3 this increase was postponed or abolished. In contrast to deltadeltaFSH, deltadeltaLH values showed the same pattern of changes in all three groups with a significant decline up to post-operative day 4 and a gradual increase thereafter. CONCLUSIONS: These results demonstrate, for the first time, that in the early to mid-luteal phase of the cycle, estradiol and progesterone participate in the control of GnRH-induced FSH, but not LH, secretion. It is possible that in the luteal phase, the response of LH to GnRH is partly regulated by gonadotrophin surge attenuating factor.