Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma.
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AIM: To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis. METHODS: Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser. RESULTS: All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone. CONCLUSIONS: The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia. (+info)
Comparison of different scoring systems for immunohistochemical staining.
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AIM: To carry out an objective assessment of two systems of scoring immunohistochemical staining, evaluating interobserver and intraobserver error. METHODS: 92 cervical tumours underwent immunohistochemical staining for p53 and epidermal growth factor receptor. Staining was assessed using two methods: a standard 4 point scale and a descriptive method, performed by three observers. Interobserver and intraobserver error were assessed for both scoring methods. RESULTS: In terms of interobserver error between three observers, no difference was found between a simple 4 point scale method of evaluation and the use of a highly circumscribed method. In all evaluations, interobserver error was scored as moderate (kappa w 0.48-0.49). However, evaluation of immunohistochemical staining by a panel of observers led to a marked improvement in the interobserver error scores (kappa w 0.63). CONCLUSIONS: There should be standardisation of immunohistochemical staining and scoring methods. More attention should be paid to measurement of interobserver and intraobserver error in studies. Use of a panel of tissue control slides and consensus scoring by several observers can lead to improvement in reproducibility. (+info)
Older women's illness representations of cancer: a qualitative study.
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This paper investigates the role of illness representations in older women's utilization of cancer screening. Older women's own beliefs, or illness representations, of cancer and cancer screening in relation to breast cancer and cervical cancer were explored using relatively unstructured, face-to-face interviews. Twenty women aged between 45 and 70 were interviewed, half of whom were regular screeners and half under-screeners. A comparison of the illness representations of the screeners with the under-screeners indicates some differences regarding cancer in general, and substantial differences regarding the treatment and cure of cancer. The screeners expressed less concern about cancer and gave more positive examples of the successful treatment of cancer. The under-screeners were more likely to express cynicism about the medical profession, to indicate that a person would have symptoms if they had cancer, that they would not want most of the treatment available for cancer, that screening is more important for younger women and that the use of alternative therapies negates the need for cancer screening. Few differences emerged between the two groups regarding the causes of cancer. (+info)
Health education to increase screening for cervical cancer among Lumbee Indian women in North Carolina.
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Although age-adjusted mortality rates from cancer among Native-Americans are generally lower than for the US population as a whole, cervical cancer mortality rates are higher. This report presents results from a National Cancer Institute-funded health education program conducted among the Lumbee tribe in North Carolina that was designed to increase the proportion of women, age 18 and older, who receive Pap smears to screen for cervical cancer. The Solomon Four Group research design was used for this project. Participants were selected at random from the enrollment records of the Lumbee tribe and data collection was carried out during face-to-face interviews. The health education program was provided one-on-one in women's homes by a trained lay health educator and included verbal, print and videotape information. A total of 979 women were enrolled in the study, and 125 were lost to follow-up between the pre-test and post-test. Women who received the education program were found to be more likely to have knowledge of the Pap smear and to report a Pap smear in the past year at the post-test than those in the control group, regardless of whether they received the pre-test interview, P < 0.05. Women most likely to respond to the education program were also likely to have reported that they receive an annual physical examination. Women with better knowledge of the Pap smear tended to have more education, higher income and greater identification with Native-American culture than those with less knowledge. We conclude that the health education program was associated with greater knowledge about cervical cancer prevention and higher proportions of Lumbee women obtaining Pap smears in the past year. (+info)
Community-based interventions to improve breast and cervical cancer screening: results of the Forsyth County Cancer Screening (FoCaS) Project.
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The FoCaS (Forsyth County Cancer Screening) Project was one of six projects funded by the National Cancer Institute "Public Health Approaches to Breast and Cervical Cancer" initiative. The goal of this project was to improve the use of breast and cervical cancer screening among low-income, predominately African-American, women age 40 and older. Strategies implemented in the intervention city included public health clinic in-reach strategies (chart reminders, exam room prompts, in-service meetings, and patient-directed literature) and community outreach strategies (educational sessions, literature distribution, community events, media, and church programs). Baseline and follow-up data from independent cross-sectional samples in both the intervention and comparison cities were used to evaluate the effects of the intervention program. A total of 248 women were surveyed at baseline, and 302 women were surveyed 3 years later at follow-up. The proportion of women reporting regular use of mammography increased (31 to 56%; P < 0.001) in the intervention city. In the comparison city, a nonsignificant (ns) increase in mammography utilization was observed (33 to 40%; P = ns). Pap smear screening rates also improved in the intervention city (73 to 87%; P = 0.003) but declined in the comparison city (67 to 60%; P = ns). These relationships hold in multivariate models. The results suggest that a multifaceted intervention can improve screening rates in low-income populations. These results have important implications for community-based research and efforts in underserved populations. (+info)
Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.
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BACKGROUND: Human papillomavirus (HPV) infection has been strongly associated with cervical carcinoma and its cytologic precursors, squamous intraepithelial lesions (SIL). We investigated the risk of SIL prospectively following polymerase chain reaction (PCR)-based DNA testing for a wide range of genital HPV types in a cohort of initially cytologically normal women, to clarify the role of HPV in the etiology of SIL. METHODS: Starting in April 1989, 17,654 women who were receiving routine cytologic screening at Kaiser Permanente (Portland, OR) were followed for the development of incident SIL. During follow-up, 380 incident case patients and 1037 matched control subjects were eligible for this nested case-control study. Cervical lavages collected at enrollment and, later, at the time of case diagnosis (or the corresponding time for selection of control subjects) were tested for HPV DNA using a PCR-based method. The data were analyzed as contingency tables with two-sided P values or, for multivariable analyses, using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In comparison with initially HPV-negative women, women who tested positive for HPV DNA at enrollment were 3.8 times (95% CI = 2.6-5.5) more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely (95% CI = 6.2-25.9) to develop high-grade SIL. At the time of diagnosis, the cross-sectional association of HPV DNA and SIL was extremely strong (OR = 44.4 and 95% CI = 24.2-81.5 for low-grade SIL and OR = 67.1 and 95% CI = 19.3-233.7 for high-grade SIL). HPV16 was the virus type most predictive of SIL, even low-grade SIL. CONCLUSIONS: These findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. Furthermore, they support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests. (+info)
Expression of vascular endothelial growth factor (VEGF) and its mRNA in uterine cervical cancers.
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To know the potential of growth, invasion and metastasis of uterine cervical cancer associated with neovascularization, localization of vascular endothelial growth factor (VEGF) and microvessel density in tumours were determined by immunohistochemical staining, the levels of VEGF subtypes were determined by Western blot analysis and by a sandwich enzyme immunoassay, and the levels of VEGF subtype mRNAs were determined by reverse transcription polymerase chain reaction (RT-PCR)-Southern blot analysis in uterine cervical cancers. The relation between VEGF subtype expressions and microvessel density, histological types and clinical stages of uterine cervical cancers was analysed. The expression of VEGF was seen dominantly in the cancer cells, and correlated with microvessel density in uterine cervical cancers. Among the four subtypes of VEGF, the populations of VEGF165 and VEGF121 were dominant in normal uterine cervices and uterine cervical cancers. The levels of VEGF and VEGF165 and VEGF121 mRNAs were remarkably higher in some stage II and III/IV adenocarcinomas of the cervix than in other cases, including normal cervices. Therefore, the elevation of VEGF165 and VEGF121 might contribute to the relatively late advancing via angiogenic activity in some adenocarcinomas of the cervix. (+info)
Inhibition of E6 induced degradation of p53 is not sufficient for stabilization of p53 protein in cervical tumour derived cell lines.
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The E6 proteins derived from tumour associated papillomavirus types target the cellular tumour suppressor protein p53 for ubiquitin mediated degradation. In cell lines derived from cervical tumours the p53 protein is present in very low amounts, but it can be activated by appropriate DNA damaging agents, indicating that functional p53 is present within these lines. Recent studies have also shown that different polymorphic forms of the p53 protein are differentially susceptible to E6 mediated degradation. Therefore we have been interested in analysing the effects of different HPV E6 proteins upon p53 levels in a variety of cervical tumour derived cell lines. We show that inhibition of E6 mediated degradation of p53 frequently results in increased levels of p53 expression. However, there are notable exceptions to this where increased p53 levels are only obtained following DNA damage and proteasome inhibition. We also show in E6 expressing cells, that as well as p53 being targeted for degradation, the localization of p53 to the nucleus is also inhibited, consistent with previous observations which indicate that degradation of p53 is not essential for E6 mediated inhibition of p53 function. These results have important implications for any potential therapies which might aim to block E6 mediated degradation of p53. (+info)