An unusual uterine tumor with signet ring cell features.

In 2004, a 56-year-old woman was diagnosed with Stage IA follicular lymphoma in a cervical lymph node biopsy. The patient experienced total remission after local radiation therapy. In 2009, a control computed tomography scan evidenced a pelvic mass, prompting total hysterectomy. The latter harbored a 4.8-cm intramural uterine tumor corresponding to a mostly diffuse and focally nodular proliferation of medium to large cells, with extensive, periodic acid-Schiff negative, signet ring cell changes, and a pan-keratin negative, CD20+, CD10+, Bcl2+, Bcl6+ immunophenotype. Molecular genetic studies showed the same clonal IGH gene rearrangement in the lymph node and the uterus, establishing the uterine tumor as a relapse of the preceding follicular lymphoma, although no signet ring cells were evidenced at presentation. Uterine localization of lymphomas is rare, and lymphomas with signet ring cell features are uncommon. This exceptional case exemplifies a diagnostically challenging situation and expands the differential diagnosis of uterine neoplasms displaying signet ring cell morphology.

An Unusual Uterine Tumor With Signet Ring Cell Features.

In 2004, a 56-year-old woman was diagnosed with Stage IA follicular lymphoma in a cervical lymph node biopsy. The patient experienced total remission after local radiation therapy. In 2009, a control computed tomography scan evidenced a pelvic mass, prompting total hysterectomy. The latter harbored a 4.8-cm intramural uterine tumor corresponding to a mostly diffuse and focally nodular proliferation of medium to large cells, with extensive, periodic acid-Schiff negative, signet ring cell changes, and a pan-keratin negative, CD20+, CD10+, Bcl2+, Bcl6+ immunophenotype. Molecular genetic studies showed the same clonal IGH gene rearrangement in the lymph node and the uterus, establishing the uterine tumor as a relapse of the preceding follicular lymphoma, although no signet ring cells were evidenced at presentation. Uterine localization of lymphomas is rare, and lymphomas with signet ring cell features are uncommon. This exceptional case exemplifies a diagnostically challenging situation and expands the differential diagnosis of uterine neoplasms displaying signet ring cell morphology.

An Integrative Genomic and Transcriptomic Analysis Reveals Potential Targets Associated with Cell Proliferation in Uterine Leiomyomas

Background: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs. Methodology: We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data. Principal Findings: The integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively) and IGFBP5 (P = 0.0002 and P = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium. Conclusions: The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs. © 2013 Cirilo et al.

Breast cancer in Mexican women: an epidemiological study with cervical cancer control

INTRODUCTION: In Mexico, breast cancer (BC) is one of the main causes of cancer deaths in women, with increasing incidence and mortality in recent years. Therefore, the aim of the study is identify possible risk factors related to BC. METHODS: An epidemiological study of hospital cases of BC and controls with cervical uterine cancer (CUCA) was carried out at eight third level concentration hospitals in Mexico City. The total of 353 incident cases of BC and 630 controls with CUCA were identified among women younger than 75 years who had been residents of the metropolitan area of Mexico City for at least one year. Diagnosis was confirmed histologically in both groups. Variables were analyzed according to biological and statistical plausibility criteria. Univariate, bivariate and multivariate analyses were carried out. Cases and controls were stratified according to the menopausal hormonal status (pre and post menopause). RESULTS: The factors associated with BC were: higher socioeconomic level (OR= 2.77; 95%CI = 1.77 - 4.35); early menarche (OR= 1.32; 95%CI= 0.88 - 2.00); old age at first pregnancy (>31 years: OR= 5.49; 95%CI= 2.16 - 13.98) and a family history of BC (OR= 4.76; 95% CI= 2.10 - 10.79). In contrast, an increase in the duration of the breastfeeding period was a protective factor (>25 months: OR= 0.38; 95%CI= 0.20 - 0.70). CONCLUSIONS: This study contributes to the identification of risk factors for BC described in the international literature, in the population of Mexican women. Breastfeeding appears to play an important role in protecting women from BC. Because of changes in women`s lifestyles, lactation is decreasing in Mexico, and young women tend not to breastfeed or to shorten the duration of lactation.

Human endometrial carcinomas serially transplanted in nude mice and established in continuous cell lines.

Three out of five human endometrial carcinomas were successfully grafted into nude mice (BALB/c/nu/nu). Two of these tumors could be maintained by serial transplantation. The morphological characteristics displayed by the grafted tumors were comparable to those of the original carcinomas. Permanent cell lines were established from these two tumors. Reinjection of cells grown in vitro into nude mice produced nodules of identical histology as compared to original solid transplants. The influence of medroxyprogesterone acetate on tumor growth in vivo and cell proliferation in vitro was studied. This hormonal treatment did not produce any significant effect on tumor cells, either in vitro or in vivo, for the two endometrial carcinomas. After medroxyprogesterone administration, a slight but non-significant growth inhibition of the tumor cells in vitro was observed and the tumor transplants in vivo did not appear to be influenced. The experiments illustrate the possible use of this model for testing potential anti-cancer agents.

Antiretroviral therapy as a factor protective against anal dysplasia in HIV-infected males who have sex with males.

OBJECTIVES Chronic infection with oncogenic HPV genotype is associated with the development of anal dysplasia. Antiretroviral therapy (ART) has been shown to decrease the incidence of cervical carcinoma in women with HIV. We sought to: 1) describe the prevalence and grade of anal dysplasia and HPV infection in our study subjects; 2) analyze the grade of correlation between anal cytology, PCR of high-risk HPV, and histology; 3) identify the factors associated with the appearance of ≥ AIN2 lesions. DESIGN Cross-sectional, prospective study. METHODS A cohort of HIV-positive males (n = 140, mean age  = 37 years) who have sex with males (MSM) had epidemiological, clinical and analytical data collected. Anal mucosa samples were taken for cytology, HPV PCR genotyping, and anoscopy for histological analysis. RESULTS Within the cohort, 77.1% were being treated with ART, 8.5% anoscopy findings were AIN2, and 11.4% carcinoma in situ; 74.2% had high-risk (HR), 59.7% low-risk (LR) HPV genotypes and 46.8% had both. The combination of cytology with PCR identifying HR-HPV better predicts the histology findings than either of these factors alone. Logistic regression highlighted ART as a protective factor against ≥ AIN2 lesions (OR: 0.214; 95%CI: 0.054-0.84). Anal/genital condylomas (OR: 4.26; 95%CI: 1.27-14.3), and HPV68 genotype (OR: 10.6; 95%CI: 1.23-91.47) were identified as risk factors. CONCLUSIONS In our cohort, ART has a protective effect against dysplastic anal lesions. Anal/genital warts and HPV68 genotype are predictors of ≥ AIN2 lesions. Introducing PCR HPV genotype evaluation improves screening success over that of cytology alone.

Prognostic factors in early-stage leiomyosarcoma of the uterus.

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 x 10). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.

The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription.

The transcriptional transactivational activities of the phosphoprotein cAMP-response element-binding protein (CREB) are activated by the cAMP-dependent protein kinase A signaling pathway. Dimers of CREB bind to the palindromic DNA element 5'-TGACGTCA-3' (or similar motifs) called cAMP-responsive enhancers (CREs) found in the control regions of many genes, and activate transcription in response to phosphorylation of CREB by protein kinase A. Earlier we reported on the cyclical expression of the CREB gene in the Sertoli cells of the rat testis that occurred concomitant with the FSH-induced rise in cellular cAMP levels and suggested that transcription of the CREB gene may be autoregulated by cAMP-dependent transcriptional proteins. We now report the structure of the 5'-flanking sequence of the human CREB gene containing promoter activity. The promoter has a high content of guanosines and cytosines and lacks canonical TATA and CCAAT boxes typically found in the promoters of genes in eukaryotes. Notably, the promoter contains three CREs and transcriptional activities of a promoter-luciferase reporter plasmid transfected to placental JEG-3 cells are increased 3- to 5-fold over basal activities in response to either cAMP or 12-O-tetradecanoyl phorbol-14-acetate, and give 6- to 7-fold responses when both agents are added. The CREs bind recombinant CREB and endogenous CREB or CREB-like proteins contained in placental JEG-3 cells and also confer cAMP-inducible transcriptional activation to a heterologous minimal promoter. Our studies suggest that the expression of the CREB gene is positively autoregulated in trans.

Reactivity spectrum of 30 monoclonal antimelanoma antibodies to a panel of 28 melanoma and control cell lines.

Thirty monoclonal antibodies from eight laboratories exchanged after the First Workshop on Monoclonal Antibodies to Human Melanoma held in March 1981 at NIH were tested in an antibody-binding radioimmunoassay using a panel of 28 different cell lines. This panel included 12 melanomas, three neuroblastomas, four gliomas, one retinoblastoma, four colon carcinomas, one lung carcinoma, one cervical carcinoma, one endometrial carcinoma, and one breast carcinoma. The reactivity pattern of the 30 monoclonal antibodies tested showed that none of them were directed against antigens strictly restricted to melanoma, but that several of them recognize antigenic structures preferentially expressed on melanoma cells. A large number of antibodies were found to crossreact with gliomas and neuroblastomas. Thus, they seem to recognize neuroectoderm associated differentiation antigens. Four monoclonal antibodies produced in our laboratory were further studied for the immunohistological localization of melanoma associated antigens on fresh tumor material. In a three-layer biotin-avidin-peroxidase system each antibody showed a different staining pattern with the tumor cells, suggesting that they were directed against different antigens.

Cigarette smoking and the risk of endometrial cancer.

The risk of endometrial cancer in relation to cigarette consumption was evaluated in a hospital-based case-control study of breast and genital neoplasms conducted in Milan, northern Italy. For the present analysis, 357 women (cases) with histologically confirmed endometrial cancer were compared to a group of 1122 women (controls) admitted for a large spectrum of acute conditions unrelated to smoking or to any of the known or potential risk factors for endometrial cancer. Compared with never-smokers, the multivariate relative risk estimates were for current 0.45 [95% confidence interval (CI) = 0.30-0.70] and 0.86 (95% CI = 0.50-1.46) for ex-smokers. The negative association of endometrial cancer with current smoking was not influenced by menopausal status as well as by other major identified potential confounding factors, i.e. menstrual and reproductive history, body mass index, oral contraceptive or estrogen replacement therapy use and family gynecologic cancer history. However, there was no evidence of a dose-risk effect, since the relative risks were similar in moderate and heavy smokers. The present study confirms that smoking is less frequent in cases hospitalized for endometrial cancer than in a comparison group of patients with non-smoking-related acute conditions. This negative association is perhaps explained in terms of reduced estrogen levels in smokers, though the influence and the importance of some uncontrolled selection bias (due, for instance, to longer hospital stay of smokers even when admission diagnosis was for non-smoking-related conditions) cannot be ruled out.

Extrauterine leiomyomata presenting with sepsis requiring hemicolectomy

Extrauterine leiomyomas are rare, benign, and may arise in any anatomic sites. Their unusual growth pattern may even mimic malignancy and can result in a clinical dilemma. Occasionally, uterine leiomyomas become adherent to surrounding structures. They also develop an auxiliary blood supply, and lose their original attachment to the uterus, thus becoming 'parasitic'. Parasitic myomas may also be iatrogenically created after uterine fibroid surgery, particularly if morcellation is used. This report presented two cases of parasitic myomas with sepsis, both requiring right hemicolectomy. It reviewed the pertinent literature.

Estratégias de intervenção utilizadas por enfermeiros da ESF do município de Natal/RN no controle do câncer do colo de útero

Cancer of the cervix (cervical cancer) is the second most prevalent cancer among Brazilian women. The high rates of cervical cancer in Brazil justify the implementation of effective strategies to control this, which include actions to promote health, primary prevention, early detection, screening, treatment and palliative care. Despite the existence of the National Programme for Control of the CCU there was no reduction in the incidence and mortality of this disease in Brazil. The Family Health Strategy (FHS) has the potential to facilitate such control and, in this context, one should consider that nurses play a central role. The study aimed to know the general intervention strategies used by nurses FHS of Natal / RN in CCU control, and how specific: analyzing the knowledge of these nurses on the CCU, the actions developed in the ESF for the control of CCU and identify the difficulties faced by them to perform it. This is a descriptive exploratory quantitative developed through a structured interview guide with 106 nurses who have experience in controlling the CCU in FHS teams of Natal / RN. Data analysis was performed using descriptive statistic s. The results pointed to actions taken in the FHS to control the CCU, collection of cervical cancer screening, health education activities, nursing consultation, referral of suspected cases for medical monitoring and active women with abnormal test result . The actions that were not mentioned by the nurses included: forming groups of prevention and health promotion; expand coverage of exams and office hours of consultations, establishment of alternatives to end the pent-up demand in the health units, participation in treatment or rehabilitation process users with the CCU; interventions for pain management, alliances and partnerships with schools, in dustry and the use of protocols. This study can be seen that the practice nurses partially shares to the CCU in Natal / RN. The participants of this study, when asked about the CCU, specifically for signs and symptoms of disease and risk factors in general showed important gaps. Difficulties such as lack of materials for collection of Pap smear; inadequate physical space in the Health Units; pent-up demand in the service, delay in arrival of the test results; obstacles in the actions of referral and counter-referral and cultural factors make the CCU control is compromised. It is believed in this research contributed to a reflection on the importance of the role of nurses in the development of the ESF control actions CCU, pointing out the factors that affect these. It is important to involve all nurses who comprise the ESF as knowledgeable of the risk factors, signs and symptoms, and existing tools for the early detection of cervical cancer in the pursuit of quality improvement actions to promote women`s health, contributing in planning future interventions that may reduce mortality from this disease in Natal / RN.

Des tumeurs fibreuses de l'utérus /

Thesis--Faculté de médecine de Paris, 1860.