RESUMO
PURPOSE OF INVESTIGATION: Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecological malignancy in the UK. The pathogenesis of this disease is poorly understood. Our hypothesis was that chlamydial infection might play a role in the pathogenesis of EOC. METHODS: 122 serum samples of patients undergoing surgery for benign or malignant gynaecological conditions were analysed. There was a total of 41 patients with EOC (33.6%), 27 with benign cystadenomas (22.1%) and 54 with normal ovaries (44.3%). RESULTS: There was a higher incidence of IgA seropositivity and lower incidence of IgG seropositivity in the EOC group compared with the other groups; however, this was not statistically significant. There was no statistical difference in the serum IgM antibodies to chlamydia in the three different groups. CONCLUSION: Although chronic infection and persistent inflammation may contribute to the pathogenesis of EOC, and chlamydia is a common genital tract pathogen, our study did not find an association between chlamydia and EOC.
Assuntos
Infecções por Chlamydia/imunologia , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/microbiologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/microbiologia , Idoso , Distribuição de Qui-Quadrado , Infecções por Chlamydia/microbiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Fatores de Risco , Reino UnidoRESUMO
BACKGROUND: Although uterine fibroids are very common, their pathogenesis and clinical behaviour are poorly understood. Since they may be prevalent in some families, we investigated whether such a prevalence was associated with distinctive clinical and molecular features. METHODS: A case-control questionnaire study of 300 multi-ethnic women with uterine fibroids at a London university hospital was undertaken, with review of case notes and immunohistochemical determination of vascular endothelial growth factor (VEGF-A) in fibroids. RESULTS: When compared with families with sporadic fibroids, familial prevalence of fibroids was associated with a higher incidence of abdominal swelling (59.1% versus 41.6%; P=0.037), menorrhagia (84.4% versus 51.9%; P=0.042), dysmenorrhoea (64.4% versus 46.3%; P=0.004), dyspareunia (43.2% versus 27.9%; P=0.012) and family history of cancers (52.3% versus 32.4%; P<0.01). The fibroids were also more multiple (mean +/- SEM: 7 +/- 0.86 versus 3 +/- 0.42; P<0.011) and strong VEGF-A expression in fibroids was more common in the familial group (64% versus 28%). Racial distribution was the same in both groups (blacks 49%, whites 33.4%, others 18.6%). CONCLUSIONS: Familial prevalence of uterine fibroids is associated with distinct clinical and molecular features that differ from those found when fibroids occur sporadically in families.
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Leiomioma/epidemiologia , Leiomioma/patologia , Adulto , Estudos de Casos e Controles , Dismenorreia/epidemiologia , Dismenorreia/metabolismo , Dismenorreia/patologia , Saúde da Família , Feminino , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Incidência , Leiomioma/metabolismo , Prevalência , Inquéritos e Questionários , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Microvessel density (MVD) in 92 paraffin sections of ovarian samples of different histologic subtypes was correlated with microvessel counts from 58 corresponding frozen sections. Anti-human von Willebrand factor antibody was used as an endothelial marker. MVD was performed in neovascular hotspots using a Quantimet 500+ Image Analyzer. The highest vessel density (HVD) and average vessel density (AVD) of three fields at the x 200 and x 400 magnification were recorded. There was a strong correlation between the HVD and AVD at the x 200 and x 400 magnifications when comparing fixed with frozen sections (correlation coefficients at x 200 for the HVD was 0.37, P = 0.005 and AVD was 0.30, P = 0.02; correlation coefficients at x 400 for the HVD was 0.38, P = 0.003 and AVD was 0.37, P = 0.004). In the fixed tissue, the HVD and AVD at both these magnifications were significantly greater in the group containing functional cysts; this was also the case for the frozen sections. These findings are consistent with the development of a microcirculation necessary for the growth and maturation of such cysts, and this appears to be greater than that in tumors. The good correlation between MVD in fixed and frozen sections suggests that such observations represent a true reflection of ovarian angiogenesis in both physiologic and pathologic states.
Assuntos
Adenocarcinoma/patologia , Cistos/patologia , Microcirculação/patologia , Neovascularização Patológica/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma/cirurgia , Feminino , Humanos , Neovascularização Fisiológica , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Ovário/cirurgia , Estudos RetrospectivosRESUMO
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.
Assuntos
Ciclina D1/biossíntese , Antígeno Ki-67/biossíntese , Ovário/citologia , Ovário/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Apoptose/fisiologia , Ciclo Celular/fisiologia , Endometriose/metabolismo , Endometriose/patologia , Endométrio/citologia , Endométrio/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologiaRESUMO
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.
Assuntos
Carcinoma de Células Escamosas/genética , Genes p53/genética , Líquen Escleroso e Atrófico/genética , Lesões Pré-Cancerosas/genética , Vulva/patologia , Neoplasias Vulvares/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/genética , Feminino , Técnicas Genéticas , Humanos , Hiperplasia/genética , Imuno-Histoquímica , Líquen Escleroso e Atrófico/patologia , Pessoa de Meia-Idade , Mutação/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Vulvares/patologiaRESUMO
BACKGROUND: Anal squamous cell carcinoma (SCC) develops from dysplastic anal warts. This study quantifies the expression of p53 and Ki67 in pre-invasive and invasive anal lesions. MATERIALS AND METHODS: Samples of 70 patients with anal warts (n = 20), low grade anal intraepithelial neoplasia (LG AIN) (n = 12), high grade anal intraepithelial neoplasia (HG AIN) (n = 27) and anal SCC (n = 11) were stained using immunohistochemical techniques. Eight patients with normal anal skin were used as controls. RESULTS: Both the expression of p53 and Ki67 increased significantly (p < 0.001) and gradually as the lesions became dysplastic and invasive. The main increase in p53 expression was as the lesions progressed from anal warts (7.38 +/- 11.93-mean +/- SD) to low grade AIN (20.778 +/- 13.14). CONCLUSION: p53 is involved in the progression of anal cancer and its expression increases from early in the development of pre-invasive anal lesions. p53 and Ki67 may be useful markers of early dysplasia and should be considered in the screening of high risk patients.
Assuntos
Neoplasias do Ânus/metabolismo , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/metabolismo , Lesões Pré-Cancerosas/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Divisão Celular/fisiologia , Progressão da Doença , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Lesões Pré-Cancerosas/patologia , Verrugas/metabolismo , Verrugas/patologiaRESUMO
INTRODUCTION: Most cases of anal carcinoma seem to develop from high grade anal intraepithelial neoplasia (AIN) caused by persistent anal warts. Similar pre-invasive epithelial genital lesions (e.g. those of the cervix and vulva) have been shown to be associated with increased angiogenesis. In this study we examined biopsies of anal lesions ranging from warts to invasive anal carcinoma, with the aim of assessing the degree of angiogenesis in pre-invasive anal lesions. METHOD: Samples from 70 patients (51 male) who had undergone excision biopsy or resection of anal wart lesions (20), low grade AIN (12), high grade AIN (27) and anal squamous cell carcinoma (SCC) (11) were studied. Samples (6) from normal HIV-anal skin were used as controls. The samples were stained for von Willebrand factor, a specific marker of endothelial cells. Angiogenesis was measured by microvessel density (MVD) analysis, quantifying the microvessels in the stroma adjacent to the epithelial lesion. RESULTS: There was a statistically significant (P < 0.001) progressive increase in MVD between low grade AIN, high grade AIN and anal SCC. The difference in MVD between normal skin, warts and low grade AIN was not statistically significant. CONCLUSION: There are progressive abnormal patterns of angiogenesis in highly dysplastic lesions, similar to those found in cervical and vulvar pathology. These findings may have biological, prognostic and therapeutic implications.
Assuntos
Canal Anal/irrigação sanguínea , Neoplasias do Ânus/patologia , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neovascularização Patológica , Neoplasias do Ânus/fisiopatologia , Carcinoma in Situ/fisiopatologia , Carcinoma de Células Escamosas/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Invasividade NeoplásicaRESUMO
Angiogenesis, the development of new blood vessels from the existing vasculature, is an essential component of solid tumour growth and metastasis. Several angiogenic factors are expressed by many tumours, suggesting that tumours promote their own vascularisation by activating the host endothelium. This review will discuss various angiogenic stimulators and inhibitors in epithelian ovarian cancer (EOC), including vascular endothelial growth factor and platelet derived endothelial cell growth factor/thymidine phosphorylase. The analysis of tumour vascularisation by microvessel density will also be discussed and the relevance of these markers of angiogenesis in the prognosis of EOC will be assessed.
Assuntos
Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/irrigação sanguínea , Indutores da Angiogênese/metabolismo , Biomarcadores Tumorais/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfocinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/patologia , Neoplasias Ovarianas/metabolismo , Prognóstico , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
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.
Assuntos
Anti-Inflamatórios/farmacologia , Antígeno Ki-67/efeitos dos fármacos , Líquen Escleroso e Atrófico/tratamento farmacológico , Proteína Supressora de Tumor p53/efeitos dos fármacos , Doenças da Vulva/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Glucocorticoides , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67/metabolismo , Líquen Escleroso e Atrófico/metabolismo , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/metabolismo , Vulva/metabolismo , Doenças da Vulva/metabolismoRESUMO
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.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Antígeno Ki-67/análise , Doença de Paget Extramamária/química , Doença de Paget Mamária/química , Proteína Supressora de Tumor p53/análise , Neoplasias Vulvares/química , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
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.
Assuntos
Sistema ABO de Grupos Sanguíneos , Carcinoma in Situ/sangue , Carcinoma in Situ/etiologia , Neoplasias Vulvares/sangue , Neoplasias Vulvares/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Reino UnidoRESUMO
Squamous cell carcinoma of the vulva (SCC) accounts for about 4% of all gynaecological malignancies. It has an incidence of about 1.8 per 100,000. However, after the age of 75 the incidence of vulvar carcinoma peaks at approximately 20 per 100,000, making it as common as cervical carcinoma. Benign and pre-malignant vulvar lesions can be broadly divided into non-neoplastic epithelial disorders of the vulva (NNEDV), vulvar intraepithelial neoplasia (VIN) and Paget's disease of the vulva (PDV). NNEDV lesions include lichen sclerosus (LS) and squamous hyperplasia (SH). To date no solid prognostic tools are available to predict which pre-malignant vulvar lesions will progress to SCC. About 4.5% of patients develop SCC following a history of LS and ca. 4% of treated VIN lesions go on to become vulvar SCC. In PDV, 28% of patients have an underlying cancer. Angiogenesis, the development of new blood vessels from existing vasculature, is an essential component of solid tumour growth and metastasis. Several angiogenic factors are expressed by many tumours, suggesting that tumours promote their own vascularisation by activating the host endothelium. This review follows the progress of research in angiogenesis in vulvar disease as assessed by a variety of methods, such as in situ hybridisation (ISH), microvessel density measurements (MVD), immunohistochemically-detected angiogenic growth factor expression, including vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), and serum concentrations of VEGF. Thus, the potential of angiogenesis as a prognostic and predictive tool for identifying which pre-malignant lesions could progress to SCC is discussed. A relatively high MVD and strong VEGF expression may serve as prognostic indicators of survival in invasive SCC. MVD and VEGF expression are also predictive factors in identifying which VIN lesions are more likely to become invasive. However VEGF is not a predictive marker in cases of LS likely to progress to carcinoma. The expression of PD-ECGF/TP in all types of lesions tested prevents its use as a prognostic tool, unlike VEGF. However, PD-ECGF/TP is involved in PDV pathogenesis, but is not a marker of the malignant progression of PDV. In PDV, VEGF was not expressed even in those cases associated with invasive disease. Serum concentrations of VEGF play a functional role in vulvar carcinogenesis. Although associated with impaired disease-free and overall survival, pre-treatment serum concentrations of VEGF are not an independent predictor of outcome in patients with vulvar cancer. These studies suggest that further angiogenic research will be important in both the therapy and prognosis of malignant and pre-malignant vulvar disease.
Assuntos
Carcinoma de Células Escamosas/irrigação sanguínea , Neovascularização Patológica/patologia , Lesões Pré-Cancerosas/irrigação sanguínea , Neoplasias Vulvares/irrigação sanguínea , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neovascularização Patológica/metabolismo , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Neoplasias Vulvares/metabolismo , Neoplasias Vulvares/patologiaRESUMO
Abnormalities in the cell cycle are associated with tumorigenesis but have not yet been identified in squamous cell carcinoma (SCC) of the vulva or in adjacent vulvar lesions. The purpose of this study was to identify cell cycle protein expression (cyclin D1 and retinoblastoma protein [pRb]) in vulvar SCC and in adjacent potentially premalignant lesions: lichen sclerosis (LS), squamous cell hyperplasia (SH), and vulvar intraepithelial neoplasia (VIN). Using immunohistochemical techniques, 57 SCCs were analyzed with 19 adjacent areas showing LS, 13 showing SH, 11 VIN, and six normal epithelium. Fifty-one percent of SCCs showed abnormal cyclin D1 expression and 37% showed abnormal pRb. Abnormal cyclin D1 expression in the adjacent areas was as follows: 53% in LS, 31% in SH, 18% in VIN, and 0% in normal. Abnormal pRb expression was as follows: 42% in LS, 62% in SH, 46% in VIN, and 33% in normal. Only 10 lesions showed abnormal expression of both proteins. Abnormal expression of cyclin D1 in SCC was statistically significant compared with adjacent normal epithelium. In SCC lesions, abnormal cyclin D1 expression was associated with greater depth of invasion. Abnormal pRb in SCC was associated with poor tumor grade. Cyclin D1 and pRb are separately involved in the progression of vulvar cancer, and changes in the expression of these proteins may represent an early stage of malignant transformation in vulvar disease.
Assuntos
Carcinoma in Situ/metabolismo , Carcinoma de Células Escamosas/metabolismo , Ciclina D1/metabolismo , Líquen Escleroso e Atrófico/metabolismo , Proteína do Retinoblastoma/metabolismo , Neoplasias Vulvares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Ciclo Celular , Transformação Celular Neoplásica/metabolismo , Feminino , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Imuno-Histoquímica , Líquen Escleroso e Atrófico/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Vulvares/patologiaRESUMO
Although uterine leiomyomas constitute the commonest benign tumour in women, the regulation of their growth is poorly understood. It is believed that angiogenesis, the process by which new capillaries develop from pre-existing blood vessels, may be involved. We therefore investigated the expression of vascular endothelial growth factor-A (VEGF-A), a primary regulator of angiogenesis, in leiomyoma tissue and the adjacent myometrium in 36 pre-menopausal women undergoing hysterectomy for leiomyomas, with or without prior treatment with gonadotrophin-releasing hormone analogue (GnRHa). In 5 microm sections prepared from archival paraffin-wax blocks, VEGF-A was demonstrated by standard immunohistochemistry using a monoclonal antibody. VEGF-A was expressed in 14 of 18 (77.8%) leiomyoma sections from women without GnRHa pretreatment, and in 15 of 18 (83%) of those from women with prior treatment. VEGF-A expression in the adjacent myometrium was much lower, being noted in two of 18 (11.1%) sections from women without prior GnRHa treatment and in one of 18 (5.5%) sections from tissue that had been subject to prior down-regulation. Moreover, when VEGF-A expression was present, expression was strong in leiomyomas (> or =20 focal areas/cm(2)), but not in adjacent myometrium. The differential expression of VEGF-A antigen in leiomyomas compared with the adjacent myometrium indicates that local angiogenesis may be important in the development and growth of these tumours. GnRHa therapy does not appear to alter this pattern of VEGF-A expression.
Assuntos
Fatores de Crescimento Endotelial/metabolismo , Leiomioma/metabolismo , Miométrio/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Antineoplásicos Hormonais/uso terapêutico , Feminino , Gosserrelina/uso terapêutico , Humanos , Leiomioma/irrigação sanguínea , Leiomioma/tratamento farmacológico , Pessoa de Meia-Idade , Neovascularização Patológica , Neoplasias Uterinas/irrigação sanguínea , Neoplasias Uterinas/tratamento farmacológico , Fator A de Crescimento do Endotélio VascularRESUMO
This pilot study investigated the use of the non-invasive cytospin monolayer technique in the diagnosis and screening of neoplastic and non-neoplastic vulval disease. Twenty-three patients (age range 34-86 years) attending a vulval disease clinic had brush cytology performed. The samples were prepared with a cytospin monolayer technique and the slides Papanicolaou-stained. Subsequent cytological interpretation and diagnosis were performed without knowledge of the clinical history and correlated with follow-up biopsy histopathology from each patient. Twenty-eight cytospin samples were analysed in total, of which 11 (39%) contained dyskaryotic cells which were assessed and a predicted VIN/AIN grade given. Ten of 11 samples (91%) reported as dyskaryotic had VIN/AIN on biopsy histology. One of 11 samples (9%) was reported as containing occasional squamous cells with borderline nuclear features and, although the corresponding biopsy did not show VIN, basal atypia was reported. One patient had features suggesting invasive carcinoma on cytology which was verified on subsequent biopsy. The 15 cases in which no dyskaryotic cells were identified did not show VIN or AIN on subsequent histology. Two cases were acellular and considered inadequate for cytological interpretation. The cytospin monolayer technique allows the diagnosis of neoplastic from non-neoplastic vulval disease. It is a quick, inexpensive and non-invasive method that may have a role in diagnosis, screening and surveillance of patients.
Assuntos
Neoplasias do Ânus/patologia , Carcinoma in Situ/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/instrumentação , Biópsia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Projetos PilotoRESUMO
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.
Assuntos
Ovário/patologia , Indução da Ovulação , Paridade , Adulto , Idoso , Estudos de Coortes , Células Epiteliais/patologia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovariectomia , Ovário/cirurgia , Lesões Pré-Cancerosas/patologia , Estudos RetrospectivosRESUMO
Lichen sclerosus (LS) has a known association with the development of squamous cell carcinoma of the vulva. The purpose of this study was to investigate molecular markers, which could indicate premalignant changes. Multiple sequential vulvar biopsies were taken over a period of 11 years from a patient with longstanding LS. Immunohistochemical staining was used to demonstrate a range of molecular markers. Increased expression of p53 and Ki67 was found in areas of squamous hyperplasia (SH) and differentiated vulvar intraepithelial neoplasia (dVIN) which correlated with the subsequent development of invasive squamous cell carcinoma (SCC). Molecular changes have been found to accompany histologic changes in the progression of vulvar LS to malignancy. Such markers may prove a useful addition in the clinical management of these conditions.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/biossíntese , Líquen Escleroso e Atrófico/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Vulvares/patologia , Adulto , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/análise , Progressão da Doença , Feminino , Genes p53/genética , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Líquen Escleroso e Atrófico/genética , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Neoplasias Vulvares/genéticaRESUMO
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.
Assuntos
Carcinoma in Situ/patologia , Líquen Escleroso e Atrófico/patologia , Neovascularização Patológica , Lesões Pré-Cancerosas/patologia , Doenças da Vulva/patologia , Neoplasias Vulvares/patologia , Carcinoma in Situ/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Líquen Escleroso e Atrófico/metabolismo , Linfocinas/metabolismo , Lesões Pré-Cancerosas/metabolismo , Timidina Fosforilase/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Doenças da Vulva/metabolismo , Neoplasias Vulvares/metabolismoRESUMO
Tumors of the pituitary gland are usually benign adenomas and account for 10% of all intracranial neoplasms. Five pituitary tumors have previously been reported to harbor multiple allelic deletions. Of these, three displayed particularly aggressive biological behavior, whereas there were no clinical details provided for the others. This study was designed to test the hypothesis that genetic deletions are a marker of invasive behavior and to identify the loci most commonly involved. Accordingly, we studied two cohorts of pituitary tumors, classified radiologically as invasive or noninvasive, for loss of heterozygosity (LOH). There is a significantly higher frequency of LOH in invasive tumors (10.8% of all loci examined) compared to noninvasive tumors (2.4%; P < 0.001). Of the 11 loci investigated, 75% of the allelic deletions identified in invasive tumors were found at 4 loci: 11q13, 13q12-14, 10q, and 1p. Twenty of 47 invasive tumors had evidence of at least 1 allelic deletion, whereas 14 of 20 had more than 1. Of the 6 tumors with only 1 deletion, 5 involved the 11q13 locus, suggesting that this is an early change in the transition from noninvasive to invasive adenoma. Comparison of invasive and noninvasive tumors demonstrates a significantly higher frequency of deletions affecting 11q13 (P < 0.001), 13q12-14 (P < 0.05), and 10q26 (P < 0.05) in invasive tumors. In addition, allelic deletion correlates with increasingly invasive behavior (modified Hardy classification), as 73% of grade 4 tumors compared to 33% of grade 3 and 9.5% of grade 1 and 2 tumors demonstrated LOH at any locus. Furthermore, in some tumors we identified a breakpoint between markers intragenic and extragenic to the retinoblastoma gene (Rb1) on chromosome 13q, suggesting that tumor suppressor genes other than or in addition to Rb1 may be involved in pituitary tumorigenesis. This was further supported by the presence of Rb protein in two of four tumors where the genetic loss extended to include the intragenic marker D13S153. Early identification of tumors with likely invasive potential by means of genetic analysis (LOH) may provide useful information on potential tumor behavior and aid tumor management in a manner that is not possible using routine histological methods. A large prospective study is required in patients without radiological evidence of invasion to assess the value of LOH in predicting outcome and for planning treatment.
Assuntos
Adenoma/genética , Adenoma/patologia , Alelos , Deleção de Genes , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adolescente , Adulto , Idoso , Biomarcadores , Mapeamento Cromossômico , Feminino , Heterozigoto , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , PrognósticoRESUMO
In the endocrine pancreas, alpha 2-adrenoceptor stimulation reduces glucose-induced insulin secretion from islet B-cells. There is, however, controversy with regard to the effects of alpha 2-agonists on islet A-cell function. In this paper, we have used RNA samples prepared from whole rat islets and from FACS-purified rat A- and B-cells to study alpha 2-adrenoceptor subtype expression. RNase protection assays detected transcripts encoding alpha 2a and alpha 2b subtypes in the RNA pool of rat islets. Reverse transcription-PCR revealed that transcripts for all three alpha 2-adrenoceptor subtypes are present in rat islet cells in purified A-cell RNA. In contrast, RT-PCR of islet B-cell RNA yielded products corresponding to alpha 2a and alpha 2c, with no evidence for the presence of alpha 2b. Thus, the results reveal that both islet cell types express more than one receptor subtype and suggest that the distribution of the subtypes may differ between rat islet A- and B-cells.