Re: "Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients".
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Disease Progression↗
Biomedical subjects
A B MacLean
Publications and source records attributed to A B MacLean.
Cell cycle and apoptotic proteins in relation to ovarian epithelial morphology.
OBJECTIVE: To assess the relationship between the expression of cell cycle and apoptotic proteins and the morphological appearance of the surface epithelium in non-neoplastic ovaries. METHODS: The subjects for this study were 79 women who had undergone oophorectomy for benign conditions at the North Middlesex Hospital, London, and Royal Free Hospital, London, and whose ovaries had been reported on routine histology as entirely normal or containing physiological cysts or endometriosis. The epithelial morphology was reassessed on haematoxylin and eosin-stained paraffin wax sections using nine cytological and architectural parameters associated with premalignant intraepithelial changes. A 'score' was obtained for each ovary. Expression of p53, Ki67, cyclin D1 and Bcl-2 in the surface, cystic and endometriotic epithelium was assessed in corresponding sections using standard immunohistochemistry. RESULTS: The median score for the morphological changes was significantly higher in the sections, which expressed p53 compared to those which did not. This difference remained significant in a subanalysis of the sections, which did not contain endometriosis. No relationship was identified between the morphological score and the expression of Ki67, Bcl-2 and cyclin D1. CONCLUSION: Increased intraepithelial abnormality as assessed by an epithelial morphological score of ovarian sections is associated with expression of the p53 cell cycle protein. This lends credence to the hypothesis that the ovarian surface or cystic epithelium goes through an identifiable precursor or "premalignant" phase before the development of invasive disease. Further work is required to characterise the changes that take place before the development of malignancy in ovarian epithelium.
Apoptosis↗
The management of Paget's disease of the vulva.
Paget's disease of the vulva is an uncommon lesion, and gynaecologists and dermatologists generally have limited experience in its management. The British Society for the Study of Vulval Disease has established a register of cases, and we present a review of 76 cases registered to date. The majority of patients were treated by surgical excision and reconstruction, but non-surgical therapies are an option. Recent literature is reviewed to allow comparison.
Aged↗
TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva.
Non-neoplastic epithelial lesions of the vulva (NNEDV) lichen sclerosus (LS) and squamous hyperplasia (SH) have been implicated in the pathogenesis of squamous cell carcinoma of the vulva (SCC). To date, there have been no recognisable precursor lesions for SCC associated with NNEDV. TP53 is the most frequent genetic change in human cancers and can indicate both aetiology and molecular pathogenesis of tumours. A total of 27 SCC patients underwent immunohistochemistry (IHC) and TP53 mutational analysis using microdissection and direct sequencing. There were 19 patients with areas of adjacent epidermis: 17 had NNEDV (four SCCs had more than one adjacent lesion) and two had normal epidermis. In all, 70.4% of the SCCs, 40% LS and 22.2% SH demonstrated overexpression of p53. In total, 77.8% of SCCs, 46.7% of LS and 22.2% SH demonstrated mutations in TP53, with the majority of lesions having a mutation in codon 136. Eight cases were identified where the same mutation was identified in the SCC and in the adjacent area. These data suggest that TP53 mutations develop in NNEDV and are intrinsic to the clonal evolution that leads to SCC. The type of mutation detected is more likely to occur due to endogenous cellular changes rather than exogenous carcinogen exposure.
Aged↗
The role of p53 and Ki67 in Paget's disease of the vulva and the breast.
OBJECTIVE: Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon diseases, accounting for approximately 1% of all vulval neoplasms and 0.5-4% of all breast cancers, respectively. In 10-30% of vulval cases an invasive adenocarcinoma is present. In such cases the disease is often aggressive and recurrence rate is high. This is in contrast to PDB where the general consensus is that almost all cases are associated with an in situ or invasive ductal carcinoma. Our aim was to examine the presence of the tumor suppressor protein p53 and the proliferation marker Ki67 in PDV and PDB and correlate any differences in the expression of these two proteins with the presence of an underlying carcinoma. METHODS: Immunohistochemistry was performed on 52 archival cases of PDV, which included 10 with associated invasive adenocarcinoma of the vulva, and on 37 archival cases of PDB, including 26 with available associated ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast. All cases were formalin-fixed and paraffin wax-embedded. Monoclonal antibodies were used with microwave antigen retrieval. Streptavidin-biotin-horseradish peroxidase and 3,3'-diaminobenzidine detection methods were employed to visualize antibody binding and staining. A section was scored positive for p53 if more than 10% of cell nuclei were stained brown and Ki67 was expressed as a percentage of positive cells to the nearest 5% of cells showing nuclear positivity (Ki67 staining index). RESULTS: p53 was expressed in 15 of 52 (29%) PDV cases and 5 of 37 (13%) cases of PDB. Four of the ten cases (40%) of PDV associated with invasive disease expressed p53 compared with 11 of 42 (26%) cases without invasive disease. The mean Ki67 staining index for PDV associated with invasion was 19%, and for that without invasion, 16%. In the breast cases, the mean staining index was 11%. CONCLUSION: Our data suggest that p53 may have a role to play in PDV progression, and may be a late event in some cases, especially those associated with invasive disease. Ki67 has no apparent prognostic role in PDV as there was no significant difference between those cases associated with and those without invasive disease. Neither p53 nor Ki67 appears to have a prognostic role to play in PDB.
Adult↗
The effect of topical corticosteroids on Ki67 and p53 expression in vulval lichen sclerosus.
BACKGROUND: Topical corticosteroids have become the treatment of choice for genital lichen sclerosus (LS) and are believed to be required for long-term relief of symptoms. OBJECTIVE: To compare vulval LS that had been treated with topical corticosteroids, vulval LS that had not received topical corticosteroids, and histologically normal vulval skin. METHODS: We used immunohistochemistry to look for Ki67 expression and abnormal p53 expression. RESULTS: We found a statistically significant difference for p53 overexpression, with increased levels seen when comparing corticosteroid-treated LS with normal genital skin (P = 0.011). Ki67 expression was also significantly higher in the corticosteroid-treated group compared with normal genital skin (P = 0.001), and increased levels were also found in the treated group compared with untreated LS (P = 0.05). CONCLUSIONS: Our data suggest that topical corticosteroids have an effect on cell cycle proteins in genital skin and, in particular, genital skin with LS changes.
Administration, Topical↗
Epithelial ovarian cancer and infertility treatment.
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Carcinoma↗
An unusual steroid-producing ovarian tumour: case report.
The rapid onset of virilization in a post-menopausal woman is usually the result of androgen secretion from a tumour of adrenal or ovarian origin. Androgen secreting neoplasms of the ovary are rare and usually show autonomous secretion. Rarely, these may be driven by the high levels of gonadotrophins seen in the post-menopausal state. We describe the case of a 67-year-old woman with high serum testosterone and estradiol in association with the high gonadotrophin levels usually associated with the post-menopausal state. All hormonal parameters showed a significant suppression over 12 h with administration of the GnRH antagonist, cetrorelix. This observation implies that excess hormone synthesis was of ovarian origin and was gonadotrophin driven. Localization of the tumour was not possible by conventional ultrasound or computerized tomography scanning, but was achieved by venous sampling. Complete cure was achieved by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with restoration of the endocrine profile to that expected for a post-menopausal woman. Rapidly acting GnRH antagonists, such as cetrorelix, offer a safe and useful diagnostic and therapeutic option in the management of ovarian steroid-secreting tumours, which show gonadotrophin dependency.
Aged↗
Is there a link between vulval cancer and blood group?
Risk factors for squamous cell vulval cancer (SCC) remain unclear though there have been associations with lichen sclerosis, smoking, and vulval intraepithelial neoplasia (VIN). We studied 191 patients who had been referred to the vulval clinic at the Royal Free Hospital and who had both blood group and histopathology results available. Seventy-two percent of patients with SCC and non-neoplastic epithelial disorders of the vulva (NNEDV) were found to be in blood group A with only 17% in blood group O. Those with SCC associated with VIN had only 30% in blood group A with 50% in blood group O. The control population showed that 38% of the population were in blood group A and 43% were in blood group O. Our results suggest that blood group A is prevalent in patients with SCC associated with NNEDV but not in those women with squamous vulval cancer and associated VIN.
ABO Blood-Group System↗
Ovarian epithelial dysplasia in relation to ovulation induction and nulliparity.
OBJECTIVE: The goal of this study was to assess the relationship between ovulation induction, nulliparity, and ovarian epithelial dysplasia. METHODS: This retrospective cohort study was performed in one teaching and one district general hospital in London. The subjects, 83 women who had undergone hysterectomy and bilateral oophorectomy and whose ovaries were reported as "normal," were divided into three groups: ovulation induction (13), nulliparity (20), and fertile controls (50). These ovaries were independently reviewed by two pathologists who assigned a score of 0, 1, or 2 to nine epithelial cytological and architectural features. The main outcome measure was the total dysplasia score, which was used to quantify the degree of ovarian epithelial abnormality in the three groups. RESULTS: The mean dysplasia score was significantly higher in the women who had undergone ovulation induction than in the fertile controls (7.92 vs 5.70, P = 0.012). The magnitude of the difference between the ovulation induction group and controls remained similar after adjusting for age, parity, and duration of oral contraceptive use (2.17, 95% CI: -0.11-4.44). However, the statistical significance of this difference was reduced (P = 0.062). We did not find any evidence of a difference in dysplasia score between nulliparous women and controls, neither before (P = 0.85) nor after adjusting for age and duration of oral contraceptive use (P = 0.87). CONCLUSIONS: These results suggest a possible association between ovarian epithelial dysplasia and ovulation induction therapy, in accord with previous reports of increased risk of ovarian cancer in women with a history of fertility treatment. The higher dysplasia score could be attributable to the drugs used to induce ovulation or to a genetic susceptibility to ovarian cancer.
Adult↗
Urinary tract infection in pregnancy.
Urinary tract infection is one of the most frequently seen 'medical' complications in pregnancy. The pioneering work of Edward Kass discovered that 6% of pregnant women had asymptomatic bacteriuria associated with increased prematurity and perinatal mortality compared to women with sterile urine. Screening for bacteriuria in pregnancy has become routine. The prevalence of asymptomatic bacteriuria as well as the associated complications described by Kass in 1962 are higher compared to most data collected in the 1980s and late 1990s in different populations in various parts of the world. Other factors such as vaginal colonization have been recognized as important contributors to preterm labour. The value of screening for bacteriuria has to be re-addressed considering methods, significance and costs. Treatment of urinary tract infection in pregnancy is critically reviewed.
Adult↗
The clinical application of a dual head gamma camera with coincidence detection in 20 women with suspected ovarian cancer.
OBJECTIVE: To assess the effectiveness of a dual head coincidence gamma camera in identifying ovarian cancer as a less expensive alternative to the traditional 2-[18F] fluoro-2-deoxy-D-glucose (18FDG) system using positron emission tomography. DESIGN: Prospective study. POPULATION: Twenty consecutive women suspected of having ovarian carcinoma. Inclusion was based on abnormal serum CA125 (reference range is 0-35 units/L), ultrasound, computerised tomography or clinical findings. METHODS: Women underwent assessment before staging laparotomy. Two nuclear medicine physicians, who were blinded to the pre-operative assessment, reported on 18FDG- dual head coincidence gamma camera imaging. MAIN OUTCOME MEASURES: The histology and operative staging were compared with the 18FDG- dual head coincidence gamma camera findings. RESULTS: Twelve women had pelvic malignancies (nine primary and three recurrences), seven women had benign pathology and one patient had a borderline malignancy. We were able to image accurately all malignant pelvic masses with dual head coincidence gamma camera, as well as accurately demonstrate disease spread. Two of the benign pelvic masses localised 18FDG. The positive predictive value for detecting malignancy was 86%. CONCLUSIONS: Dual head coincidence gamma camera offers accurate and affordable imaging in suspected ovarian masses, with improved specificity over CA125, ultrasound and computerised tomography. These results are similar to those obtained on more expensive dedicated PET systems. We report on a series of patients believed to have primary or recurrent carcinoma and recognise the need to include patients more likely to have benign lesions to assess false positive results. However, we believe that dual head coincidence gamma camera is useful in the pre-operative assessment of women with suspected ovarian cancer.
Adult↗
Paget's disease of the vulva.
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Journal Article↗
Role of angiogenesis in benign, premalignant and malignant vulvar lesions.
OBJECTIVE: To investigate the presence of angiogenic factors in benign, premalignant and malignant vulvar lesions. STUDY DESIGN: Immunohistochemical demonstration of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in normal vulvar skin, lichen sclerosus, vulvar intraepithelial neoplasia (VIN) and vulvar cancer. RESULTS: VEGF was found in the majority of vulvar cancers but only a minority of VIN lesions. PD-ECGF was found in the majority of lesions. CONCLUSION: Demonstration of angiogenesis may suggest which preinvasive lesions will progress to invasive cancer.
Carcinoma in Situ↗
Ovarian cancer and infertility: a genetic link?
A genetic mechanism may be responsible for the increased incidence of ovarian cancer in some infertile women (ie, those who failed to conceive despite treatment).
Case-Control Studies↗
Assessment of response to treatment in vulvar vestibulitis syndrome by means of the vulvar algesiometer.
OBJECTIVE: A pilot study was undertaken to investigate the utility of the vulvar algesiometer in correlating symptom improvement with treatment response. STUDY DESIGN: Women with a diagnosis of vulvar vestibulitis syndrome attending a specialist vulvar clinic were assessed with the vulvar algesiometer before and after treatment. RESULTS: The conditions of 25 patients had improved to the point of discharge, and readings from before and after treatment were compared. There was a statistically significant difference in the vulvar algesiometer readings before and after treatment and this improvement was reflected in patient response. Nine patients had no response to treatment and also no significant improvement in vulvar algesiometer score. CONCLUSION: The vulvar algesiometer provides an easy noninvasive means of assessing vestibular tenderness in vulvar vestibulitis syndrome that is well tolerated by the patients and provides a degree of biofeedback for them.
Female↗
An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina.
OBJECTIVE: To map potential sites of sex steroid action in the human vulva. METHODS: Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stain frozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to compare receptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma. RESULTS: Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hair follicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora than in vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginal epithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin. They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of the skin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest in suprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smooth muscle but not in the vulva. There was no evidence of significant differences in androgen or oestrogen receptor staining in the vulva of pre- or postmenopausal women. CONCLUSION: The transition from vagina to vulva is marked by an increase in androgen and a decrease in oestrogen and progesterone receptors. This distribution of receptors would indicate a limited role for oestrogen creams on the vulva.
Adult↗