Fernandes Figueira Institute Fiocruz

Fernandes, Brazil

Fernandes Figueira Institute Fiocruz

Fernandes, Brazil

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Russomano F.B.,Fernandes Figueira Institute Fiocruz | De Camargo M.J.,Fernandes Figueira Institute Fiocruz | Machado Gayer C.R.,State University of Rio de Janeiro | Santos-Reboucas C.B.,State University of Rio de Janeiro | Brito Macedo J.M.,State University of Rio de Janeiro
International Journal of Gynecological Pathology | Year: 2013

High-risk human papillomaviruses are closely associated with cervical cancer and its precursor lesions through interactions between the E6 and E7 oncoproteins and the cell-cycle regulatory proteins, such as p53 and pRb, respectively. As other molecules involved in the cell-cycle control seem to be important for human papillomavirus (HPV)-mediated cervical carcinogenesis, we have analyzed the expression of p53, p21, p16, cyclin D1, and Ki-67 and the presence of HPV (HPV pool and HPV-16) by immunohistochemical studies using tissue microarray in low squamous intraepithelial lesions (n=50), high squamous intraepithelial lesions (n=98), and cervical carcinoma (n=18). We have found a significant increase in the expression of p16 and p21 (P<0.001) from low- to high-grade lesions and cancer. In contrast, cyclin D1 expression showed a significant decrease in more severe lesions (P<0.001). p16, Ki-67, p21, and p53 positivity increased with the cell-layer level and the lesion severity, with stronger correlations being observed for p16 and Ki-67. High positivity for HPV pool (96.3%) and HPV-16 (77.5%) immunostaining was detected in all cases, with an association between p16 and cyclin D1 expression and HPV-16 infection. Our tissue microarray results corroborate the usefulness of the immunohistochemical assessment of cell-cycle biomarkers in distinguishing different groups of precursor lesions of the cervix and cervical carcinoma. © 2013 International Society of Gynecological Pathologists.


Monteiro D.L.M.,State University of Rio de Janeiro | Monteiro D.L.M.,Jacarepagua Hospital | Trajano A.J.B.,State University of Rio de Janeiro | Russomano F.B.,Fernandes Figueira Institute FIOCRUZ | And 2 more authors.
Journal of Pediatric and Adolescent Gynecology | Year: 2010

Our objective was to describe the evolution of cervical SIL within 24 months of the initial diagnosis, in a cohort study of 147 sexually active adolescents attending a public health service in Rio de Janeiro, between 1993 and 2006. The participants were divided in two groups, according to whether cervical biopsy was performed or not. The median of the interval between sexual debut and the atypical cytopathology was 12 months and in 8.2% of patients there was a diagnosis of HSIL at the first abnormal smear. After a two-year follow-up by cytology, the regression (ASCUS 91%, LSIL 63.6%, HSIL 50%) and progression (LSIL 6.1%) were verified. In the group undergoing biopsy, the final histological regression reached 59.4% for CIN1 and 71.4% for CIN2, while the progression from CIN1 to CIN 2/3 was 3.1%. Our results corroborate the recommendation for conservative management in compliant adolescents due to a high regression rate. However, there should be maintained a careful follow-up based on the possible evolution of the lesion. © 2010 North American Society for Pediatric and Adolescent Gynecology.


Monteiro D.L.M.,State University of Rio de Janeiro | Sodre D.C.B.,FEBRASGO | Russomano F.B.,Fernandes Figueira Institute FIOCRUZ | Trajano A.J.B.,State University of Rio de Janeiro | Silva K.S.,Fernandes Figueira Institute FIOCRUZ
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2013

Objectives: To estimate the incidence of genital warts in adolescents and analyze their relationship with the development of cervical squamous intraepithelial lesions (SIL). Study design: From 1993 to 2006 we followed 846 adolescents in the gynecology clinic of a public hospital in Rio de Janeiro. They were sexually active, had a normal smear test and no genital warts upon recruitment and completed two years of follow-up. Data were analyzed using EPI-INFO software. The research was approved by the hospital Ethics Committee. Results: The mean age at recruitment was 15.8 ± 1.4 years and at first intercourse was 14.7 ± 1.6. Sixty-three (7.4%) adolescents presented condylomata, 5.6% (48/846) during the first year of sexual activity and 1.8% (15/846) during the second year. Within two years, 20.5% (174/846) of the patients had an abnormal smear test. Seventy percent (44/63) of the patients with genital warts developed a SIL. The association between warts and SIL showed a RR = 4.2(3.3-5.3). Conclusions: The incidence of condylomatawas one third of the incidence of SIL and was higher during the first than in the second year of sexual activity. Adolescents with genital warts had a fourfold increase in risk of SIL and therefore should be carefully followed up. © 2013 Elsevier Ireland Ltd. All rights reserved.


Furtado Y.L.,Post University | Almeida G.,Post University | Lattario F.,Federal University of Rio de Janeiro | Silva K.S.,Fernandes Figueira Institute Fiocruz | And 5 more authors.
Diagnostic Molecular Pathology | Year: 2010

Methylation is a chemical modification in which a methyl group (CH3) is added to the cytosine in the promoter region of the gene. It involves a very frequent epigenetic event that is found in many human cancers. Currently, there is no consensus on whether methylation of the p16 gene could be used as a biomarker in cervical intraepithelial neoplasia. The authors studied the presence of methylation of the p16 gene and human papillomavirus (HPV) DNA, and a possible relationship between them in high-grade squamous intraepithelial lesions of the cervix. This case-control study analyzed 27 high-grade squamous intraepithelial lesion samples and 20 normal cytology samples. To detect p16 methylation, methylation-specific polymerase chain reaction was used, and for HPV DNA detection the polymerase chain reaction was performed by using MY09/MY11 and GP5+/GP6+ consensus primers. The presence of methylation of the promoter region of the p16INK4a gene was detected in 55.6% of the samples from the case group, whereas it was detected only in 20% of the samples from the control group (P=0.005). HPV DNA was found in 66.7% of the samples from the case group, whereas only 15% from the control group (P=0.0001). The relationship between the presence of methylation of the p16 gene and HPV DNA did not prove statistically significant in the case group (P=0.67) or the control group (P=0.51). In conclusion, the presence of methylation of the p16 gene constituted an occurrence that was early but independent of the presence of HPV DNA. Copyright © 2010 by Lippincott Williams & Wilkins.


Vargas-Torres S.L.,State University of Rio de Janeiro | Portari E.A.,State University of Rio de Janeiro | Portari E.A.,Fernandes Figueira Institute FIOCRUZ | Klumb E.M.,State University of Rio de Janeiro | And 4 more authors.
Biomarkers | Year: 2014

Variants of p16(INK4a) and p14(ARF), encoded by the CDKN2A locus, may respond differently to the presence of human papillomavirus (HPV). We investigated the potential association of two CDKN2A polymorphisms, 500C>G (rs11515) and 540C>T (rs3088440), with cervical neoplasia in patients with cervical lesions and healthy controls (n=492). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and/or DNA sequencing techniques were employed for genotyping. The 500G allele was found higher, whereas the 540T/T genotype was less frequent in patients with more severe lesions. The CDKN2A variants may have the potential to be markers for the management of patients with cervical neoplasia. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.


Crispi C.P.,Fernandes Figueira Institute FIOCRUZ | De Souza C.A.P.,Fernandes Figueira Institute FIOCRUZ | De Souza C.A.P.,Federal University of São Paulo | Oliveira M.A.P.,Fernandes Figueira Institute FIOCRUZ | And 7 more authors.
Journal of Minimally Invasive Gynecology | Year: 2012

Study Objective: To demonstrate the prevalence of endometriosis in the intrapelvic portion of the round ligaments of the uterus (RLUs) and to propose criteria for their excision. Design: Retrospective case series analysis of women undergoing laparoscopy for the treatment of deep infiltrating endometriosis (Canadian Task Force classification II-3). Setting: Tertiary referral hospital. Patients: We evaluated 174 patients who underwent laparoscopy for the treatment of deep infiltrating endometriosis (DIE) between April 2006 and May 2009. Interventions: All patients underwent laparoscopy for the treatment of DIE and had their RLUs removed when there was shortening, deviation, or thickening. After removal, the RLUs were sent for histopathologic analysis to verify the presence or absence of endometriosis. Measurements and Main Results: The prevalence of endometriosis in the RLUs and the association between the macroscopic alterations and the anatomic pathology results were determined. After the identification of macroscopic alterations, 1 or both RLUs (for a total of 42) were removed from 27 of the 174 patients who underwent laparoscopy. The positive predictive value (PPV) of the macroscopic criteria proposed for endometriosis of the RLU was 83.3% (95% confidence interval [CI] = 72.1%-94.5%), with 35 positive RLUs out of the 42 that were excised. The prevalence of endometriosis of the RLU was 13.8% (95% CI = 8.7%-18.9%), with 24 patients having a positive histopathologic examination result for endometriosis. Conclusions: The prevalence of RLU endometriosis in patients with DIE was 13.8%, which emphasizes that a rigorous evaluation of this structure must be part of the routine surgical treatment of patients with endometriosis. © 2012 AAGL.


Vargas-Torres S.L.,State University of Rio de Janeiro | Portari E.A.,State University of Rio de Janeiro | Portari E.A.,Fernandes Figueira Institute FIOCRUZ | Silva A.L.,State University of Rio de Janeiro | And 6 more authors.
Tumor Biology | Year: 2016

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38–0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39–0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32–0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions. © 2016 International Society of Oncology and BioMarkers (ISOBM)


Cruz A.C.,State University of Rio de Janeiro | Neves B.C.,Federal University of Rio de Janeiro | Higa L.Y.S.,Fernandes Figueira Institute FIOCRUZ | Folescu T.,Fernandes Figueira Institute FIOCRUZ | And 2 more authors.
APMIS | Year: 2012

Pseudomonas aeruginosa is associated with increased mortality in cystic fibrosis (CF) patients, and expresses type III secretion system proteins (TTSP), which is a common mechanism used by gram-negative pathogens for delivery of anti-host factors. Our aim was to investigate whether or not these antigens (TTSP) would be recognized by CF sera, by Western blot reaction. We have showed herein that all patients (n = 11) not chronically infected by P. aeruginosa had their first serum positive for TTSP (ExoS, ExoT, PopB, and/or PopD). All chronic patients had a strong positive serology to TTSP, although relatively weak reactions to TTSP were observed for some individuals in the negative control group. Therefore, TTSP that were early produced in P. aeruginosa infected CF patients, induced a detectable antibody response in those patients and were easily detected by Western-blot reaction. © 2012 The Authors APMIS © 2012 APMIS.


PubMed | State University of Rio de Janeiro and Fernandes Figueira Institute FIOCRUZ
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR=0.60; 95% CI=0.38-0.95; p=0.029; CA+AA vs CC genotype: OR=0.60; 95% CI=0.39-0.93; p=0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR=0.55; 95% CI=0.32-0.93; p=0.034) by 50%, representing a protective factor against the development of more severe cervical lesions.


PubMed | Fernandes Figueira Institute FIOCRUZ
Type: Journal Article | Journal: Journal of minimally invasive gynecology | Year: 2011

To demonstrate the prevalence of endometriosis in the intrapelvic portion of the round ligaments of the uterus (RLUs) and to propose criteria for their excision.Retrospective case series analysis of women undergoing laparoscopy for the treatment of deep infiltrating endometriosis (Canadian Task Force classification II-3).Tertiary referral hospital.We evaluated 174 patients who underwent laparoscopy for the treatment of deep infiltrating endometriosis (DIE) between April 2006 and May 2009.All patients underwent laparoscopy for the treatment of DIE and had their RLUs removed when there was shortening, deviation, or thickening. After removal, the RLUs were sent for histopathologic analysis to verify the presence or absence of endometriosis.The prevalence of endometriosis in the RLUs and the association between the macroscopic alterations and the anatomic pathology results were determined. After the identification of macroscopic alterations, 1 or both RLUs (for a total of 42) were removed from 27 of the 174 patients who underwent laparoscopy. The positive predictive value (PPV) of the macroscopic criteria proposed for endometriosis of the RLU was 83.3% (95% confidence interval [CI] = 72.1%-94.5%), with 35 positive RLUs out of the 42 that were excised. The prevalence of endometriosis of the RLU was 13.8% (95% CI = 8.7%-18.9%), with 24 patients having a positive histopathologic examination result for endometriosis.The prevalence of RLU endometriosis in patients with DIE was 13.8%, which emphasizes that a rigorous evaluation of this structure must be part of the routine surgical treatment of patients with endometriosis.

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