Expression of cyclooxygenase-2 (COX-2) and Ki67 as related to disease severity and HPV detection in squamous lesions of the cervix.

OBJECTIVES: To assess the expression of cyclooxygenase (COX-2) and Ki67 in cervical squamous lesions in relation to disease severity and human papillomavirus (HPV) detection. SUBJECTS AND METHODS: For this cross-sectional study, 223 women subjected to diathermic conization of the cervix have been enrolled, between February 2001 and April 2004. All patients undertook pelvic examination, including colposcopy and collection of samples for Hybrid Capture II (HCII). Pathological assessment disclosed: 9 cases of normal epithelium/cervicitis, 33 CIN1, 28 CIN2, 146 CIN3 and 7 invasive squamous cell carcinomas. COX-2 and Ki67 protein expression was determined with immunohistochemistry. COX-2 immunoreactivity grading was based on the German ImmonoReactive score. The continuum percentage of positive cells was used for the assessment of nuclear Ki67 expression. RESULTS: Expression of COX-2 did not correlate with disease severity and with Ki67 expression. The HPV detection rates did not differ significantly across COX-2 protein expression strata, ranging from negative to strong expression. Ki67 expression, however, was higher in the CIN3 group (P = 0.001) as compared to the specimens rendered as normal/cervicitis. CONCLUSIONS: COX-2 protein expression did not correlate with disease severity or Ki67 expression.

Telomerase activity in cervical intraepithelial neoplasia.

BACKGROUND: It was reported that telomerase expression is closely associated with cellular immortality and cancer. This study was designed to investigate the relationship between telomerase expression and the carcinogenesis of cervical cancer, the possible use of telomerase as a marker of cervical intraepithelial neoplasia (CIN) progression or regression, and the natural history of CIN. METHODS: Telomeric repeat amplification protocol (TRAP) assay was used to measure telomerase activity in cervical scrapings and biopsy samples obtained from 105 cases affected with various cervical conditions, including chronic cervicitis (n = 20), CIN (n = 64, 16 cases of CIN I, 20 cases of CIN II, and 28 cases of CIN III), and invasive squamous cell carcinoma (n = 21). RESULTS: In exfoliated cell samples, telomerase activity was detected in 5 of 20 (25.0%) cases of cervicitis, 10 of 16 (62.5%) cases of CIN I, 11 of 20 (55.0%) cases of CIN II, 23 of 28 (82.1%) cases of CIN III, and 13 of 21 (61.9%) cases of carcinoma. In cervical biopsy samples, telomerase activity was detected in 6 of 20 (30.0%) cases of cervicitis, 8 of 16 (50.0%) cases of CIN I, 9 of 20 (45.0%) cases of CIN II, 27 of 28 (96.4%) cases of CIN III, and 20 of 21 (95.2%) cases of carcinoma. Telomerase activation was significantly higher in CIN samples than in cervicitis samples. Telomerase activity was detected at similar frequency in samples from cervical scrapings and cervical biopsies. CONCLUSION: These results seem to suggest that telomerase expression may be associated with carcinogenesis of the cervix. TRAP assay of cervical scraping samples could be used to monitor and predict the development of CIN in clinical practice.

Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological cervical cancer screening.

OBJECTIVE: This study aims at exploring the potential use of telomerase activity assay and typing of human papillomaviruses (HPV) 16 and 18 in improving the identification of high-grade cervical intraepithelial neoplasia (CIN). METHODS: From 86 women with normal cervical smears and from 114 patients with abnormal cervical smears cervical scrapings were collected. The telomerase activity was assayed using the Telomerase Repeat Amplification Protocol, and HPV was detected using consensus primers and specific primers for HPV 16 and HPV 18. RESULTS: HPV 16 in cervical scrapes was significantly associated with high-grade squamous epithelial lesions on cytology and with high-grade CIN, i.e., CIN 2/3 on biopsy. The detection of HPV 18 or telomerase activity had no significant association with high-grade squamous intraepithelial lesions or high-grade CIN. CONCLUSION: The use of the telomerase activity assay in cervical scrapes, unlike HPV 16 typing, did not improve the detection of high-grade CIN.

Elevated lipid peroxidation and disturbed antioxidant enzyme activities in plasma and erythrocytes of patients with uterine cervicitis and myoma.

OBJECTIVES: We investigated whether oxidative stress is associated with human uterine cervicitis and uterine myoma. DESIGN AND METHODS: We measured lipid peroxidation and antioxidant enzymes in plasma and erythrocytes of cervicitis patients and myoma patients in comparison with matched controls. Thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, were determined in plasma; glutathione peroxidase (GSHPx) and catalase in erythrocytes; and superoxide dismutase (SOD) in both plasma and erythrocytes. RESULTS: We showed that plasma TBARS were significantly higher (p < 0.05) in both cervicitis patients and myoma patients than in controls. Plasma TBARS were significantly (and negatively) correlated with plasma and erythrocyte T-SOD activities in cervicitis patients only. Plasma T-SOD activity was significantly lower in both groups of patients than in controls whereas erythrocyte T-SOD activity was only significantly lower in myoma patients. The lowered plasma T-SOD activity in the cervicitis patients was attributed to decreased Mn-SOD activity whereas the lowered plasma T-SOD activity in myoma patients was attributed to decreased activities of both Cu,Zn-SOD and Mn-SOD. Erythrocyte GSHPx activity was 14% higher (p < 0.05) in cervicitis patients and 11% lower (p > 0.05) in myoma patients than in controls; catalase activity was 10% higher (p > 0.05) in cervicitis patients and 13% lower (p > 0.05) in myoma patients than in controls. Neither erythrocyte GSHPx nor catalase activity was significantly correlated with plasma TBARS. CONCLUSIONS: The elevated lipid peroxidation and disturbed antioxidant enzyme activities demonstrate the potential of oxidative injury in patients with uterine cervicitis and myoma.

The usefulness of screening for chlamydial trachomatis infection with cervical mucus leukocyte esterase.

OBJECTIVE: To evaluate the ability of leukocyte esterase dipstick test (LET) performed in cervical mucus to predict direct immunofluorescent (DIF)-verified Chlamydia trachomatis (Ct) cervical infection. METHOD: Eighty women with inflammatory cervico-vaginal smear were submitted to both an endocervical smear, to verify Ct cervicitis by DIF technique; and a cervical mucus sample to perform LET. Results of LET and DIF were matched. RESULTS: Among 30 Chlamydial positive subjects, cervical mucus esterase test was positive in 28 (93.3%); while among 50 Chlamydial negative controls, esterase test was negative in 43 subject (86%). The sensitivity, specificity, positive and negative predictive values for LET were 93.3%, 86%, 80% and 95% respectively. CONCLUSION: Cervical mucus LET is a simple, cost effective screening test, with promising accuracy, for Ct cervical infection among women with inflammatory cervico-vaginal smears.

[Intravaginal bacterial flora and clinical significance of granulocyte elastase and pH determination].

In 95 patients with abnormal vaginal and cervical secreta (49 pregnant women and 46 non-pregnant women), the relation between intravaginal flora and intravaginal granulocyte elastase (Elastase) and pH was investigated. The results were as follows. 1) Gram-positive bacteria were detected in the vaginal secreta at a high rate (87/144, 60.4%), and it mainly consisted of Lactobacillus sp. (67/142, 46.5%). It was followed anaerobia (26/144, 18.1%) and fungi (26/144, 18.1%). 2) The patients with cervicitis or vaginitis had higher elastase value (6.65-6.69 micrograms/ml) than the ones with vaginal erosion, and the patients who showed an intravaginal pH value not lower than 5.0 had significantly increased elastase value (6.44 +/- 1.40 micrograms/ml) than the patients who showed the values 4.5 or higher. 3) Regarding the relation between the detected bacteria and elastase values, elastase values were higher in the patients infected by anaerobia (6.58 +/- 1.40 micrograms/ml), Gram-negative bacteria (6.01 +/- 3.61 micrograms/ml), Gram-positive bacteria (5.02 +/- 0.94 micrograms/ml) and fungi (5.14 +/- 1.08 micrograms/ml) than the values in patients with Lactobacillus sp. (pH < 4.5). Further, the intravaginal pH value was higher than 4.5 in all of these groups, which was higher compared with the one in the patients infected with Lactobacillus sp. (4.04 +/- 0.04).

Leukocyte esterase dipstick as a rapid screening test for vaginitis and cervicitis.

STUDY OBJECTIVE: To assess the ability of vaginal and cervical leukocyte esterase (LE) dipstick to detect vaginitis and cervicitis. DESIGN: A prospective, cross-sectional study to assess the ability of the LE dipstick of vaginal secretions to detect trichomonads, candida, and bacterial vaginosis and the LE dipstick of vaginal and cervical secretions to detect gonococcal and chlamydia infection and polymorphonuclear cells (PMNs). SETTING: An inner-city shelter facility clinic. PARTICIPANTS: 183 sexually active, nonmenstruating females aged 13-21 years (Mean = 17.7, SD = 1.98 years): 47% black, 40% white, and 11% Hispanic. OUTCOME MEASURES: Sensitivity (SN), specificity (SP), positive and negative predictive values (PVP, PVN), with 95% confidence intervals, of vaginal and cervical LE dipstick > or = trace in detecting vaginal and cervical infections. RESULTS: A positive vaginal LE had a moderately high SN and PVN but poor SP and PVP in detecting trichomonas and candida vaginitis and bacterial vaginosis. A positive vaginal and cervical LE had a high SN and PVN but poor SP and PVP in detecting gonorrhea and chlamydia infection. A positive cervical LE had a moderate SN and low SP in detecting PMNs on Gram stain. CONCLUSIONS: The LE dipstick of vaginal and cervical secretions was only a moderately good screening test for vaginal infection but a good screening test for cervical infection.

Cytochemical evaluation of gamma-glutamyl-transpeptidase activity in cervical smears.

The cervicovaginal smears of 43 patients attending an outpatient service for early cancer detection were cytochemically studied for the presence of gamma-glutamyl-transpeptidase (GGT) in epithelial cells. This was done in order to evaluate such an enzyme phenotype as a marker for cancer development. The results showed that 70% of the 38 patients with a cytologic diagnosis of "inflammatory" or preneoplastic/neoplastic conditions had GGT-positive cells in their smears. None of the five cytologically normal cases showed any epithelial cells with GGT activity. Although most of the GGT-positive cells were metaplastic, some morphologically normal, dysplastic or neoplastic cells also expressed the enzyme. The data suggest that cytochemically detectable transpeptidase activity appears whenever alterations of the normal epithelial microenvironment occurs, but is not necessarily linked to the carcinogenic process. Therefore, cytochemically GGT-positive cells should not be used as an indicator of neoplastic transformation of the cervical epithelium.

Histoenzymological study on desquamative cervico-vaginal cells.

Dihydrofolate dehydrogenase activity was histochemically investigated comparatively to the activities of 6-phosphogluconate, glucose-6-phosphate, malate and lactate dehydrogenases, NADH-2-tetrazolium dehydrogenase, esterases, beta-glucuronidase and leucyl aminopeptidase in smears of desquamative cervico-vaginal cells of negative and positive Papanicolaou classes. Dihydrofolate dehydrogenase was found active in a greater percentage of cells and stronger in individual cells of cervical carcinoma than in normal, inflammatory or dysplastic cervix uteri. The other enzymes activities were less specifically increased in dyskaryotic cells.