LUISA LINA VILLA

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Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder

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Autor e Coautores FMUSP-HC Normalizados: ADHEMAR LONGATTO FILHO ×

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  • article 9 Citação(ões) na Scopus
    Critical Analyses of the Introduction of Liquid-Based Cytology in a Public Health Service of the State of Sao Paulo, Brazil
    (2015) LONGATTO-FILHO, Adhemar; LEVI, Jose Eduardo; MARTINS, Toni Ricardo; COHEN, Diane; CURY, Lise; VILLA, Luisa Lina; ELUF-NETO, Jose
    Objective: The aim of this study was to compare the performance of the current conventional Pap smear with liquidbased cytology (LBC) preparations. Study Design: Women routinely undergoing their cytopathological and histopathological examinations at Fundacao Oncocentro de Sao Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of Sao Paulo with similar sociodemographic characteristics. Results: A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells -cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the twomethods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of highgrade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). Conclusions : LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs. (C) 2015 S. Karger AG, Basel
  • conferenceObject
    TISSUE EXPRESSION OF SUPEROXIDE DISMUTASE-2 AS A MARKER OF INTRAEPITELIAL NEOPLASIA AND INVASIVE CERVICAL CARCINOMA
    (2015) RABELO-SANTOS, S. H.; VILLA, L. L.; TERMINI, L.; LONGATTO, A.; ANDREOLI, M. A.; ANGELO-ANDRADE, L. A. L.; DERCHAIN, S.; ZEFERINO, L. Carlos
  • article 30 Citação(ões) na Scopus
    Self-collection for high-risk HPV detection in Brazilian women using the caFeHPV (TM) test
    (2013) LORENZI, Adriana Tarla; FREGNANI, Jose Humberto T. G.; POSSATI-RESENDE, Julio Cesar; NETO, Cristovam Scapulatempo; VILLA, Luisa Lina; LONGATTO-FILHO, Adhemar
    Objective. Cervical cancer is the second most common cancer among Brazilian women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause of cervical neoplasia. Early detection of hr-HPV is important for identifying women at risk for developing cervical lesions. Approximately 85% of new cases of cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in developing countries. Here, a new methodology to support a cervical cancer screening program was evaluated in women from various Brazilian regions. Methods. Two thousand women aged 18-77 years were enrolled in an opportunistic cervical cancer screening program and were randomized into self-vaginal or health professional-guided cervical sampling groups. The Qiagen careHPV (TM) test was performed on all samples. Pap tests were performed on all women using liquid-based cytology. Results. Positive hr-HPV results were obtained in 12.3% (245/2000) of women; similar rates were observed in self- or health professional-collected samples. Eighty-nine percent (1719/2000) of cervical cytologies classified as normal were negative to hr-HPV. Among the cytological samples, 36.6% classified as ASC-US + were positive to hr-HPV, 78.8% were LSIL and 75.0% were HSIL. Conclusions. Self-sampled and health professional-sampled vaginal/cervical specimens did not differ in their rates of detection of hr-HPV. Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to primary screening in low-resource settings.
  • article 11 Citação(ões) na Scopus
    High-Risk HPV Testing in Primary Screening for Cervical Cancer in the Public Health System, Sao Paulo, Brazil
    (2019) LEVI, Jose Eduardo; MARTINS, Toni Ricardo; LONGATTO-FILHO, Adhemar; COHEN, Diane Dede; CURY, Use; FUZA, Luiz Mario; VILLA, Luisa L.; ELUF-NETO, Jose
    Every year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of Sao Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to I IPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class >= ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papillomavirus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7,2% of the women. Per protocol, 1,592 Hr-HPV+ women, in addition to 72 patients with cytologic classification > low-grade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2(+)) cases were diagnosed, 79 were Hr-HPV DNA(+) and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3(+) cases were Hr-HPV DNA(+). HPV genotyping may be useful in the management of Hr-HPV+ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3(+). Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.
  • conferenceObject
    Molecular analysis of RAS genes mutations in patients with cervical adenocarcinoma.
    (2015) GARCES, Alvaro Henrique Ingles; INADA, Haynna Kimie Pimenta; MORA, Paulo; TORRES, Michelle; ALMEIDA, Fabio Marques de; LONGATTO-FILHO, Adhemar; VILLA, Luisa Lina; MOREIRA, Marise Amaral Rebouas; FERREIRA, Carlos G. M.; MELO, Andreia Cristina De
  • article 4 Citação(ões) na Scopus
    A positive HPV test with positive p16/Ki-67 double staining in self-sampled vaginal material is an accurate tool to detect women at risk for cervical cancer
    (2022) LORENZI, Noely P. C.; TERMINI, Lara; FERREIRA-FILHO, Edson S.; NUNES, Rafaella A. L.; SILVA, Gabriela A. F.; LEPIQUE, Ana P.; LONGATTO-FILHO, Adhemar; TACLA, Maricy; BARACAT, Edmund C.; VILLA, Luisa L.; SOARES-JUNIOR, Jose M.
    BACKGROUND: The development of efficient strategies for managing high-risk human papillomavirus (HR-HPV)-positive women is a major challenge when human papillomavirus-based primary screening is being performed. The objectives of this study were to evaluate the comparative effectiveness of HR-HPV testing based on self-collection (SC) and HR-HPV testing based on collection by a health professional (HP) and to assess the potential usefulness of HR-HPV testing combined with testing with the biomarkers p16/Ki-67, alpha-mannosidase, and superoxide dismutase 2 (SOD2). METHODS: This was a cross-sectional study of 232 women admitted for colposcopy because of an abnormal Papanicolaou smear. The collected material underwent liquid-based cytology, HR-HPV detection, and immunocytochemical testing (p16/Ki-67, alpha-mannosidase, and SOD2). The gold standard was the histopathological result; the positive reference was CIN2+. RESULTS: The overall accuracy of HR-HPV testing was 76.6%; the results for the SC group (78.1%) and the HP group (75.2%) were similar. The positive predictive values (HP, 76.5%; SC, 80.0%), the negative predictive values (HP, 66.7%; SC, 64.3%), the positive likelihood values (HP, 1.35; SC, 1.36), and the negative likelihood values (HP, 0.21; SC, 0.19) were also similar. p16/Ki-67 showed higher sensitivity than the other 2 biomarkers: 78.1% versus 45.8% for alpha-mannosidase and 44.5% for SOD2. The specificities of the biomarkers were equivalent: 71.4% for p16/Ki-67, 77.8% for alpha-mannosidase, and 71.2% for SOD2. In the HP group, accuracy also leaned more heavily toward the final score (using alpha-mannosidase and SOD2) without statistical significance (80.8% vs 77.9%). The contrast with the SC group yielded the same level of accuracy. CONCLUSIONS: SC, when associated with testing with biomarkers, is as accurate as collection by HPs in the detection of women at risk for cervical cancer.
  • article 26 Citação(ões) na Scopus
    SOD2 immunoexpression predicts lymph node metastasis in penile cancer
    (2015) TERMINI, Lara; FREGNANI, Jose H.; BOCCARDO, Enrique; COSTA, Walter H. da; LONGATTO-FILHO, Adhemar; ANDREOLI, Maria A.; COSTA, Maria C.; LOPES, Ademar; CUNHA, Isabela W. da; SOARES, Fernando A.; VILLA, Luisa L.; GUIMARAES, Gustavo C.
    Background: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown. Methods: SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis. Results: SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis. Conclusions: Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.
  • article 31 Citação(ões) na Scopus
    MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis
    (2015) DISCACCIATI, Michelle G.; GIMENES, Fabrcia; PENNACCHI, Paula C.; FAIAO-FLORES, Fernanda; ZEFERINO, Luiz C.; DERCHAIN, Sophie M.; TEIXEIRA, Julio C.; COSTA, Maria C.; ZONTA, Marco; TERMINI, Lara; BOCCARDO, Enrique; LONGATTO-FILHO, Adhemar; CONSOLARO, Marcia E. L.; VILLA, Luisa L.; MARIA-ENGLER, Silvya S.
    Background: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. Methods: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. Results: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). Conclusions: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. Impact: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis. (C) 2015 AACR.
  • conferenceObject
    Role of Monocarboxylate Transporters (MCTs) in the Regulation of the Metabolic Profile of Cervical Cancer Cells by Hypoxia
    (2012) PINHEIRO, C.; SANTOS, F.; MIRANDA-GONCALVES, V.; BOCCARDO, E.; LEPIQUE, A. P.; LONGATTO-FILHO, A.; VILLA, L. L.; BALTAZAR, F.
    Background: Due to the high growth rates of some tumors, cells are exposed to hypoxia, leading to a metabolic switch from oxidative phosphorylation to glycolysis. High glycolytic rates, in turn, lead to production of important amounts of lactate, which are exported to the extracellular milieu, contributing to the acidic microenvironment. Low oxygen concentrations lead to stabilization of hypoxia-inducible factor 1 alpha (HIF-1a), which regulates the expression of several glycolytic markers, as well as pH regulators. Thus, monocarboxylate transporters (MCTs) by mediating the co-transport of lactate with a proton, allow the maintenance of the glycolytic phenotype and intracellular pH, contributing to the tumour acidic microenvironment. However, MCT regulation by hypoxia is not fully understood, being sometimes controversial such as the case of MCT1. Aims: We aimed to characterize the expression of MCT1 and MCT4 and other glycolytic markers, as well as lactate transport activity under hypoxia conditions. The sensitivity of uterine cervix tumour cells to the MCT1 inhibitor CHC (a-cyano-4-hydroxycinnamic acid) was compared between normoxic and hypoxic conditions. Material and Methods: Hypoxia was induced by incubation of human cervical cancer cell lines in a hypoxic chamber (<1% O2). Expression of MCT1, MCT4, CD147, GLUT-1, CAIX and LDH was evaluated by immunocytochemistry and Western blot. Glycolytic metabolism was assessed through quantification of glucose consumption and lactate production. The effect of CHC on cell biomass was performed through the Sulforhodamine B assay. Results and Discussion: In general, the expression of the glycolytic metabolic markers GLUT-1, CAIX and LDH increased with hypoxia, which was accompanied by an increase in MCT1 expression in C33 cells and increased plasma membrane expression of MCT1 of SiHa cells. However, the expected increase in MCT4 expression was not observed. Interestingly, the expression of the MCT1/4 chaperone CD147 decreased in C33 and SiHa cells, pointing to the possible association with a different chaperone. Consistent with the increase in MCT1 expression, the sensitivity to CHC decreased in hypoxic conditions. Conclusion: We showed that hypoxia upregulates the expression of MCT1 in cervical cancer cells, rather than MCT4, and decreased the sensitivity to the MCT1 inhibitor CHC. These findings provide evidence for MCT regulation by hypoxia in cervical cancer and for the role of MCT1 in glycolytic metabolism. Acknowledgements: Part of this work was supported by FAPESP-São Paulo Research Foundation: 2008/03232−1 and the FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of 'Programa Operacional Temático Factores de Competitividade' (COMPETE) of ‘Quadro Comunitário de Apoio III’ and co-financed by Fundo Comunitário Europeu FEDER.
  • article 30 Citação(ões) na Scopus
    Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas
    (2015) PINHEIRO, Celine; GARCIA, Eduardo A.; MORAIS-SANTOS, Filipa; MOREIRA, Marise A. R.; ALMEIDA, Fabio M.; JUBE, Luiz F.; QUEIROZ, Geraldo S.; PAULA, Elbio C.; ANDREOLI, Maria A.; VILLA, Luisa L.; LONGATTO-FILHO, Adhemar; BALTAZAR, Fatima
    Background: Deregulation of cellular energetic metabolism was recently pointed out as a hallmark of cancer cells. This deregulation involves a metabolic reprogramming that leads to a high production of lactate. Lactate efflux, besides contributing for the glycolytic flux, also acts in the extracellular matrix, contributing for cancer malignancy, by, among other effects, induction of angiogenesis. However, studies on the interplay between cancer metabolism and angiogenesis are scarce. Therefore, the aim of the present study was to evaluate the metabolic and vascular molecular profiles of cervical adenocarcinomas, their co-expression, and their relation to the clinical and pathological behavior. Methods: The immunohistochemical expression of metabolism-related proteins (MCT1, MCT4, CD147, GLUT1 and CAIX) as well as VEGF family members (VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3) was assessed in a series of 232 cervical adenocarcinomas. The co-expression among proteins was assessed and the expression profiles were associated with patients' clinicopathological parameters. Results: Among the metabolism-related proteins, MCT4 and CAIX were the most frequently expressed in cervical adenocarcinomas while CD147 was the less frequently expressed protein. Overall, VEGF family members showed a strong and extended expression with VEGF-C and VEGFR-2 as the most frequently expressed and VEGFR-1 as the less expressed member. Co-expression of MCT isoforms with VEGF family members was demonstrated. Finally, MCT4 was associated with parametrial invasion and HPV18 infection, CD147 and GLUT1 with distant metastasis, CAIX with tumor size and HPV18 infection, and VEGFR-1 with local and lymphnode metastasis. Conclusions: The results herein presented provide additional evidence for a crosstalk between deregulating cellular energetics and inducing angiogenesis. Also, the metabolic remodeling and angiogenic switch are relevant to cancer progression and aggressiveness in adenocarcinomas.