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Central giant cell granulomas (CGCG) of the jaws are osteolytic lesions that may behave aggressively and respond poorly to surgery. Microscopically, in addition to giant cells, there is a mononuclear cell population composed of macrophage/monocytic cells and spindle-shaped cells of mesenchymal origin. Seventy two percent of these tumours harbour mutually exclusive TRPV4, KRAS and FGFR1 mutations. We aimed to assess the mutational status of mononuclear and giant cells and the osteogenic potential of stromal cells in vitro and in vivo.We screened CGCG for signature mutations and used laser-capture microdissection to demonstrate that the mutations are restricted to the mononuclear cells. Additionally, we established CGCG primary cell culture and observed that the cells retained the mutations throughout passages. By flow cytometry, we observed predominance of CD14Collectively, the results confirm that the signature mutations are restricted to stromal cells in CGCG, and the in vitro and in vivo results support that these cells have the capacity to differentiate into osteoblasts, in line with the bone formation often observed in the stroma of these lesions.

This narrative review aimed to evaluate the effectiveness of PDT in early or advanced squamous cell carcinoma of the head and neck (SCCHN). Scopus, MEDLINE/PubMed, and Embase were searched electronically following the PRISMA protocol. Quality assessment was performed according to JBI, NIH, and AMSTAR protocols. The main outcomes evaluated were treatment response, recurrence, survival, and adverse effects. A total of 49 articles met the search criteria: 43 case series, two cohort studies, two prospective before-after clinical trials, one systematic review, and one meta-analysis. Data from 2121 SCCHN patients were included. The response to PDT was variable according to the type of photosensitizer, tumor location, and tumor stage. In general, higher complete responses rated were observed in T1/T2 SCCHN, mainly with mTHPC-mediated PDT. With regard to T3/T4 or advanced SCCHN tumors, there is no compelling evidence suggesting the effectiveness of PDT. Any adverse effects reported were well tolerated by patients. The present review suggests that PDT is a promising treatment modality for early-stage SCCHN. Although there are limitations due to the low level of evidence of the included studies, we believe that the present review could help to design robust clinical trials to determine the efficacy of PDT in SCCHN.

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

Objectives The aim of this study was to evaluate the histomorphologic presentation and the expression of stem cell–related markers in a series of oral solitary fibrous tumors (SFTs). Study Design Histopathological variables and the expression of the standard stem cell markers CD34 and CD99, used for SFT diagnosis, as well as STAT6 were evaluated in 13 oral SFTs. The expression of the cancer stem cell markers CD44, ALDH1, Bmi-1, and Nanog and the tumor suppressor gene p16Ink4a were also investigated. Results The majority of oral SFTs were circumscribed and characterized by a proliferation of spindle cells arranged in a hyalinized stroma. Only 2 oral SFTs showed >4 mitoses/10 high-power fields. Hypercellularity as well as nuclear and cellular pleomorphism were classified as low and moderate in most of the oral SFTs. All oral SFTs were positive for CD34, STAT6, CD44, ALDH1, Bmi-1, and p16Ink4a. CD99 and Nanog expression was observed in 11 and 10 oral SFT cases, respectively. Conclusion We suggest that STAT6 and ALDH1 have relevant diagnostic value. The expression of CD44, ALDH1, Bmi-1, and Nanog, which is observed in cancer stem cells, may confer advantages to oral SFT cells.

Made available in DSpace on 2022-04-29T08:41:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT). Materials and Methods: Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression of CYP1A1, GSTM1, GSTP1, and GSTT1 genes by the RT-qPCR method. Results: There were significant differences in the AUDIT score and CYP1A1 expression between cancer and control groups. Participants in advanced stages, whether due to tumor size or regional metastasis, showed significant differences in the duration of tobacco use, FTCD, AUDIT score, and CYP1A1 expression when compared to patients in early stages. Among subjects without cancer, we found a significant correlation between participant age and GSTP1 expression. Furthermore, the expression of GSTP1 was significantly correlated with the number of cigarettes smoked per day, duration of tobacco use, and FTCD. Conclusions: Questionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies. Department of Bioscience and Oral Diagnosis Institute of Science and Technology of São José dos Campos São Paulo State University (Unesp) Faculdade de Ciências Médicas de São José dos Campos—Humanitas School of Medicine Anhembi Morumbi University Technology Research Center (NPT) Universidade Mogi das Cruzes Department of Head and Neck Surgery São Leopoldo Mandic College Department of Head and Neck Surgery Hospital Municipal Doutor Mário Gatti Department of Basic Sciences and Environment São Paulo University Department of Oral Pathology School of Dentistry São Paulo University Department of Bioscience and Oral Diagnosis Institute of Science and Technology of São José dos Campos São Paulo State University (Unesp) FAPESP: #2016/08633-0

Made available in DSpace on 2020-12-12T02:46:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Objective: The aim of this study was to evaluate the expression of DNA repair genes in cases of oral squamous cell carcinoma (OSCC). Study Design: Expression of the MLH1, MSH2, MLH3, ATM, MRE11A, XRCC1, and PMS2 genes was evaluated by reverse transcription–quantitative polymerase chain reaction in the OSCC group (32 patients) and the control group (15 patients). The groups were compared by using the Mann-Whitney test, with Bonferroni correction. Associations between gene expression levels and clinical data were explored by using Pearson's and Spearman's correlation coefficients, with P value less than. 05 indicating a significant difference. Results: The MLH1, MSH2, MLH3, ATM, MRE11A, XRCC1, and PMS2 genes were downregulated in the OSCC group compared with the control group, with significant values for MLH1 (P < .0001); MSH2 (P = .038); MLH3 (P < .0001); ATM (P < .0001); MRE11A (P < .0001); XRCC1 (P = .0004); and PMS2 (P = .008). Analysis of the correlation between gene expression and clinical data only revealed a significant negative correlation between age and expression of the PMS2 gene. Conclusions: Expression of the DNA repair genes MLH1, MSH2, MLH3, ATM, MRE11 AMRE11A, XRCC1, and PMS2 was reduced in OSCC. School of Dentistry Universidade Mogi das Cruzes School of Dentistry Brazcubas Educação Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Head and Neck Surgery São Leopoldo Mandic Medical School Department of Head and Neck Surgery Hospital Municipal Dr. Mário Gatti Department of Oral Pathology School of Dentistry University of São Paulo School of Medicine Anhembi Morumbi University São José dos Campos Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP)

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

To investigate the expression of upstream and downstream targets of mTOR signalling pathway in the secretory carcinoma of salivary gland origin (SCsg). Seven cases of secretory carcinoma diagnosed by a combination of immunohistochemistry and/or molecular testing were retrieved from our pathology files. For comparison purposes, 27 other salivary carcinomas were selected. Immunohistochemical staining was performed against phospho-Akt, PTEN, phospho-mTOR, phospho-4E-BP, eIF4E and phospho-S6 ribosomal protein. With the exception of Akt, all the other proteins were present at some level in the SCsg and in other salivary carcinomas. PTEN was diffusely expressed in 57.1% of SCsg, but only in 14.8% of other salivary carcinomas. mTOR is expressed in more than half of the cases both for SCsg and other salivary tumour types. Most cases of SCsg showed negative expression for S6 ribosomal protein (71.4%) and 4E-BP1 (57.1%). For both groups evaluated, eIF4E was the most expressed protein. SCsg shows different expression patterns for the mTOR signalling molecules, but only eIF4E was highly expressed. This may suggest alternative signalling pathways other than Akt and mTOR in this group of tumours.

Oral cancer squamous cell carcinoma (OCSCC) mainly affects individuals aged between 50 and 70 years who consume tobacco and alcohol. Tobacco smoke contains hundreds of known toxic and carcinogenic molecules, and a few studies have sought to verify the relationship of such trace elements as risk or prognostic factors for head and neck cancer. We obtained 78 samples of tumor tissues from patients with OCSCC, and performed a qualitative elemental characterization using the micro X-Ray Fluorescence technique based on synchrotron radiation. We found the presence of magnesium, phosphorus, sulfur, chlorine, potassium, calcium, chromium, manganese, iron, zinc, cobalt, nickel, copper, arsenic and bromine in OCSCC samples. Magnesium, chlorine, chromium, manganese, nickel, arsenic and bromine are associated with smoking. We observed a significant association between relapse and chlorine and chromium. The presence of chlorine in the samples was an independent protective factor against relapse (OR = 0.105, CI = 0.01–0.63) and for best disease-free survival (HR = 0.194, CI = 0.04–0.87). Reporting for the first time in oral cancer, these results suggest a key relationship between smoking and the presence of certain elements. In addition, chlorine proved to be important in the context of patient prognosis and survival.

Cancer is currently a major public health problem worldwide, with a marked increase of about 70% in the number of expected diagnosed cases over the next two decades. The amount of tobacco and alcohol consumed is calculated based on the subjective information provided by the user. Tobacco exposure can be assessed using the Fagerström Test for Cigarette Dependence (FTCD) and alcohol consumption by the Alcohol Use Disorder Identification Test (AUDIT).Forty-eight subjects answered the Fagerström, and AUDIT tests and we studied them as likely screening tools for oral cancer and their correlation with the expression ofThere were significant differences in the AUDIT score andQuestionnaires designed to evaluate the degree of tobacco and alcohol exposure and dependence combined with gene expression tests can be useful to assess the risk of developing oral cancer. Furthermore, raising the awareness of individuals regarding their degree of dependence and encouraging them to participate in cessation programs are important educational measures for the prevention of tobacco-related malignancies.

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

OBJECTIVE This study investigated components of the Hedgehog (HH) signaling pathway (SHH, GLI1), cyclin D1, and smooth muscle actin (SMA) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. MATERIAL AND METHODS Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. RESULTS Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared with the other proteins (P

L.K. is a fellow in the Canadian Institutes of Health Research (CIHR) Strategic Training in Advanced Genetic Epidemiology (STAGE) programme and is supported by the CIHR Doctoral Research Award from the Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-137441). Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by the National Institutes of Health (U19-CA148127, CA148127S1). Genotyping for the TRICL-ILCCO OncoArray was supported by in-kind genotyping at Centre for Inherited Disease Research (CIDR) (26820120008i-0–6800068-1). Genotyping for the Head and Neck Cancer OncoArray performed at CIDR was funded by the US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780–0. CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03–0365 and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02–67 and FICYT IB09–133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Publica. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health (NIH)/National Cancer Institute (NCI): UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989 (PI Doherty). The Liverpool Lung Project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578 and CA074386. The Multiethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464 and CA148127. The work performed in MSH-PMH study was supported by the Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997) and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. Dr Melinda Aldrich is supported by the by NIH/National Cancer Institute 5K07CA172294. The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Kentucky Lung Cancer Research Initiative (KLCRI) was supported by the Department of Defense (Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Command Program) under award number: 10153006 (W81XWH-11–1-0781). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The research undertaken by M.D.T., L.V.W. and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The Tampa study was funded by Public Health Service grants P01-CA68384 and R01-DE13158 from the National Institutes of Health. The University of Pittsburgh head and neck cancer case–control study is supported by US National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; grants 04/12054–9 and 10/51168–0). The authors thank all the members of the GENCAPO team. This publication presents data from the Head and Neck 5000 study. The study was a component of independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707–10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission’s fifth framework programme (QLK1– 2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97–0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (01/01768–2). The IARC Central Europe study was supported by the European Commission’s INCO-COPERNICUS Program (IC15-CT98–0332), US NIH/National Cancer Institute grant CA92039 and World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662 and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.

Background Most patients with head and neck cancer receive nonsteroidal anti-inflammatory drugs concomitant with oncogenic treatment in order to control cardiovascular diseases and chronic inflammatory processes. Inflammation is closely related to neoplastic development and the release of inflammatory cytokines and chemokines represents a crucial event in this relationship. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) and celecoxib treatment in the gene expression pattern of cytokines and chemokines in squamous cell carcinoma (OSCC) cell lines. Materials and methods Cells were treated with plasmatic concentrations of ASA and celecoxib and were submitted to cell viability assay and immunoenzymatic assay to investigate interleukin 6 (IL6) production. Treated cells were collected and a gene expression array was performed using the reverse transcriptase-quantitative polymerase chain reaction. Results Both treatments provoked a discrete inhibitory effect on cell viability and modulated IL6 production. The mRNA expression of several cytokines, chemokines, chemokine receptors, and other chemotaxis-related genes were modulated after treatment with ASA and celecoxib. Conclusion Plasmatic doses of ASA and celecoxib altered the expression of IL6 and the gene expression of chemokines (ligands and receptors) and cytokines in a dose- and time-dependent manner.

Objectives Investigate the DNA copy number and the methylation profile of the homeobox genes HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, HOXC13, HOXD10, HOXD11, IRX4 and ZHX1, and correlate them with clinicopathological parameters and overall survival. Material and methods DNA from OSCC samples and surgical margins were submitted to DNA amplification by qPCR and to DNA methylation analysis using a DNA Methylation PCR Array System. Results HOXA5, HOXB5 and HOXD10 were amplified in surgical margins while HOXA9, HOXB13 and IRX4 were amplified in OSCC. HOXD10 demonstrated hypermethylation in half of the tumor while ZHX1 did not show hypermethylation. No correlation of DNA copy number or methylation with clinicopathological parameters or survival was observed. Conclusion HOXA9, HOXB13 and IRX4 genes appears to be regulated by amplification and HOXD10 by methylation in OSCC. Further studies are needed to determine the role of these events in OSCC development.

Introduction Immune cells contribute with mediators in the protein expression profile of the tumor microenvironment. Levels of plasminogen activator inhibitor-1 (PAI-1) are elevated in non-malignant inflammatory conditions; however, the association between PAI-1 expression and inflammation remains uncertain in oral squamous cell carcinoma (OSCC). This study aimed to investigate PAI-1 expression in mononuclear inflammatory cell infiltrate in OSCC and its role as a prognostic marker. Methods Samples were collected from patients with OSCC, treated surgically, and followed for 24 months after the procedure. Thirty-nine tumoral tissue were analyzed using immunohistochemistry. Correlation between protein expression, clinicopathological parameters, and the prognosis was investigated. Results Positive PAI-1 expression in mononuclear inflammatory cell infiltrate was significantly associated with lymph node status (p = 0.009) and with the cytoplasmic expression of vascular endothelial growth factor A (VEGFA) (p = 0.028). Multivariate analysis revealed weak PAI-1 expression as an independent marker for lymph node metastases, with approximately 8-fold increased risk compared to strong expression (OR = 8.60; CI = 1.54–48.08; p = 0.014). Conclusion Our results suggest that the strong PAI-1 expression in intratumoral inflammatory infiltrate is an indicator of a better prognosis for patients diagnosed with oral squamous cell carcinoma., Highlights • PAI-1 is a potential marker for lymph node metastasis in the OSCC with predictive potential of the marker under metastatic conditions.

This study evaluated the optical absorbance spectrum of human monocytes, neutrophils and lymphocytes polarized, or not, to the inflammatory or immunoregulatory phenotypes. Peripheral human blood leukocytes were isolated and polarized (10 ng/mL) with LPS or IL-4 + LPS for 2 hours. After polarization, cells were washed and incubated for an additional 24 hours (monocytes and lymphocytes) or 12 hours (neutrophils). Next, cells were collected to evaluate the optical absorbance spectrum. The three types of leukocytes exhibited absorbance in the region from 450 to 900 nm, with greater absorbance at wavelengths lower than 570 nm. Lymphocytes had a second region of greater absorbance between 770 and 900 nm. Inflammatory monocytes and lymphocytes showed increased absorbance of blue, green and yellow wavelengths (monocytes), as well as red and infrared wavelengths (monocytes and lymphocytes). Immunoregulatory polarization altered the absorbance of monocytes and lymphocytes very little. Neutrophils treated with LPS or LPS + IL-4 exhibited lower absorbance at wavelengths higher than 575 nm compared to untreated cells. The present findings showed that leukocytes exhibit greater absorbance in regions of the spectrum that have not been much used in photobiomodulation (PBM), and the polarization of these cells can affect their capacity to absorb light. Taken together, these results suggest new perspectives in the use of PBM in the clinical setting depending on the wavelengths and the stage of the inflammatory process.

Advanced salivary gland mucoepidermoid carcinoma (MEC) is a relentless cancer that exhibits resistance to conventional chemotherapy. As such, treatment for patients with advanced MEC is tipically radical surgery and radiotherapy. Facial disfigurement and poor quality of life are frequent treatment challenges, and many patients succumb to loco-regional recurrence and/or metastasis. We know that cancer stem-like cells (CSC) drive MEC tumorigenesis. The current study tests the hypothesis that MEC CSC are sensitive to therapeutic inhibition of mTOR. Here, we report a correlation between the long-term clinical outcomes of 17 MEC patients and the intratumoral expression of p-mTOR (p = 0.00294) and p-S6K1 (p = 0.00357). In vitro, we observed that MEC CSC exhibit constitutive activation of the mTOR signaling pathway (i.e., mTOR, AKT, and S6K1), unveiling a potential strategy for targeted ablation of these cells. Using a panel of inhibitors of the mTOR pathway, i.e., rapamycin and temsirolimus (mTOR inhibitors), buparlisib and LY294002 (AKT inhibitors), and PF4708671 (S6K1 inhibitor), we observed consistently dose-dependent decrease in the fraction of CSC, as well as inhibition of secondary sphere formation and self-renewal in three human MEC cell lines (UM-HMC-1,-3A,-3B). Notably, therapeutic inhibition of mTOR with rapamycin or temsirolimus induced preferential apoptosis of CSC, when compared to bulk tumor cells. In contrast, conventional chemotherapeutic drugs (cisplatin, paclitaxel) induced preferential apoptosis of bulk tumor cells and accumulation of CSC. In vivo, therapeutic inhibition of mTOR with temsirolimus caused ablation of CSC and downregulation of Bmi-1 expression (major inducer of stem cell self-renewal) in MEC xenografts. Transplantation of MEC cells genetically silenced for mTOR into immunodeficient mice corroborated the results obtained with temsirolimus. Collectively, these data demonstrated that mTOR signaling is required for CSC survival, and unveiled the therapeutic potential of targeting the mTOR pathway for elimination of highly tumorigenic cancer stem-like cells in salivary gland mucoepidermoid carcinoma.

Made available in DSpace on 2018-12-11T17:22:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-08-29 Background: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. Methods: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. Results: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. Conclusions: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas. Departamento de Biologia Molecular Faculdade de Medicina (FAMERP), Av. Brigadeiro Faria Lima, 5416, Vila São Pedro Departamento de Biologia Instituto de Biociências Letras e Ciências Exatas (IBILCE) Universidade Estadual Paulista (UNESP), R. Cristóvão Colombo, 2265 Instituto Do Câncer de São Paulo Octavio Frias de Oliveira - ICESP, Av. Dr. Arnaldo, 251 - Cerqueira César Faculdade Ceres (Faceres), Av. Anísio Haddad, 6751 Departamento de Estomatologia Faculdade de Odontologia Universidade de São Paulo, Av. Prof. Lineu Prestes, 2227 Instituto Do Câncer Arnaldo Vieira de Carvalho, R. Dr Cesário Mota Jr, 112 Departamento de Cirurgia de Cabeça e Pescoço Hospital Heliópolis, R. Cônego Xavier, 276 Departamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas Universidade de São Paulo, Avenida do Café, s/n Departamento de Genética e Biologia Evolutiva Instituto de Biociências Universidade de São Paulo, R. do Matão, 321 Departamento de Biologia Instituto de Biociências Letras e Ciências Exatas (IBILCE) Universidade Estadual Paulista (UNESP), R. Cristóvão Colombo, 2265

Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti‐inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL‐6,TNF‐α and TGF‐β mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF ‐β mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.

O Plano Nacional de Pós-Graduação recomenda que o Sistema Nacional de Pós-Graduação desenvolva estudos tendo em vista as necessidades e os interesses dos estudantes da educação básica. Buscando seguir esta diretriz, o Programa de Pós-Graduação em Ciências Odontológicas da Faculdade de Odontologia da Universidade de São Paulo estabeleceu uma parceria com instâncias gestoras da rede pública de educação no município de São Paulo, formulando e implementando o projeto Experimentando Ciência. O objetivo foi de aproximar os estudantes do ensino fundamental do conhecimento científico produzido na universidade, promovendo a popularização da ciência e da tecnologia. A partir da delimitação de um problema em sala de aula, quatro grupos de dez alunos, percorriam cinco laboratórios da faculdade, com o objetivo de levantar hipóteses, ensaiar e testar desenhos experimentais. Participaram, ao longo do ano de 2016, cinco escolas, perfazendo um total de 200 alunos. Os resultados foram apresentados em conjunto na forma de relatórios, relatos de experiência, e divulgados para a comunidade escolar, no sentido de compartilhar e multiplicar o conhecimento. De acordo com os relatos, os estudantes tiveram a oportunidade de ampliar o entendimento da ciência de forma prática, instigando a curiosidade pela pesquisa e despertando a percepção de que a educação superior é uma etapa possível de ser alcançada no ciclo educacional. Para a universidade, o projeto demonstrou a viabilidade e importância da articulação interdisciplinar e entre os diferentes níveis educacionais.

Oral squamous cell carcinoma (OSCC) is the most prevalent neoplasia of oral cavity worldwide and prognosis remains unchanged in decades. Recently, different authors reported that head and neck squamous cell carcinomas have a subpopulation of tumor initiating cells that apparently correspond to cancer stem cells (CSC) and are also responsible for tumor growth and metastasis. The purpose of the present study was to investigate the microscopic and phenotypic characteristics of OSCC tumors induced after orthotopic xenoimplantation of SCC9WT cell line and CSC-enriched subpopulation isolated from SCC9 cell line based on high expression of the putative CSC marker CD44. Different numbers of FACS-sorted SCC9 CD44high and CD44low cells as well as SCC9WT (wild type) were transplanted into the tongue of BALB/C nude (NOD/SCID) mice to evaluate their tumorigenic potential. Sixty days post-induction, tumors were morphologically characterized and immunostained for CSC markers (CD44, Nanog and Bmi-1), epithelial-mesenchymal transition (Snail, Slug) and epithelial differentiating cell markers (cytokeratins 4, 13, 15, 17 and 19), as well as E-cadherin and β-catenin. The data presented here shows that SCC9 CD44high cells have higher ability to form tumors than SCC9 CD44low cells, even when significantly lower numbers of SCC9 CD44high cells were transplanted. Immunoassessment of tumors derived from SCC9 CD44high cells revealed high expression of cytokeratin CK19, β-catenin, E-cadherin and CD44, and negative or low expression of CK17, CK4, CK15, CK13, Nanog, Bmi-1, Snail and Slug. While tumors derived from SCC9WT showed high expression of CK17, CK19, CD44, Nanog, Bmi-1, Snail and Slug, and negative or low expression of CK4, CK15, CK13, β-catenin and E-cadherin. Thus, SCC9 CD44high cells were highly tumorigenic, capable of originating heterogeneous tumors and these tumors have a immunohistochemical profile different from those formed by the wild type cell line.

Made available in DSpace on 2018-12-11T17:23:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. Materials and methods The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with p

Objective: This study aimed to show schoolchildren the variety of microorganisms present before and after hand hygiene, and to make them aware of the transmission and autoinoculation of pathogenic microorganisms. Study design: This study was approved by ethical committee and is part of the "Projeto Experimentando Ciencia." A total of 27 volunteers from 5 different public schools, aged from 11 to 15 years, participated in this study. A microbiota sample was collected using sterile swab and Sabouraud dextrose agar plates before and after hand hygiene orientation (World Health Organization [WHO] technique 1). After 1 week, plates were shown and explained to the participating children. Different materials were used for hand hygiene in each school. Results: A total of 35% used water and paper towels to sanitize the hands; 32% used water, soap and paper towels; 30% used only water; and 3% used soap and water. A larger variety and number of colonies were found before sanitization than after, even in the group that washed hands only with water. Fungi such as Penicillium, Aspergillus, Cladosporium, and nonsporulated types, as well as bacteria, were identified on the samples. One week after the procedure, teachers reported children changed their hand hygiene habits. Conclusion: Visualization of fungi and bacteria culture improved schoolchildren hand hygiene.

Radiographic examinations complement the anamnesis and physical exam with the purpose of reaching diagnosis, prognosis and treatment planning. In this case report, a 48 year-old male Caucasian patient was referred to an oral and maxillofacial surgeon by a general practitioner after a panoramic radiography for treatment planning; the implant surgery follow-up portrayed a multilocular radiolucent image at the left posterior mandible. Based solely on the panoramic radiography, the diagnostic hypothesis was ameloblastoma. The surgeon decided to perform an incisional biopsy. However, during the procedure, the professional noted that the lesion was easily detached from the adjacent bone and opted for the total removal of the lesion, thus altering its diagnostic hypothesis to central ossifying fibroma (COF). The histopathological result confirmed the diagnostic hypothesis provided by the surgeon, i.e. COF. Although multilocular presentation is not common, COF should be considered in the scope of multilocular radiolucent lesions of the jaws. In addition, computerized tomography imaging exam complemented by surgical and histopathological aspects should be considered for establishing the final diagnosis and conducting the therapeutic approach.

In response to stimuli in the microenvironment, macrophages adopt either the M1 or M2 phenotype to coordinate the tissue repair process. Photobiomodulation (PBM) plays an important role in the modulation of acute inflammation, including cellular influx, macrophage polarization, and the release of inflammatory mediators. The aim of the present study was to evaluate the effects of red and infrared PBM on the mRNA expression of cytokines and chemokines in macrophages polarized to the M1 and M2 phenotypes. J774 macrophages activated to induce M1 (lipopolysaccharide + interferon gamma) or M2 (interleukin-4) phenotypes were irradiated with red or infrared PBM (1 J). After 4 and 24 h, gene expression was analyzed by qPCR. PBM at 660 nm decreased the mRNA expression of CCL3, CXCL2, and TNF-α in M1 macrophages and CXCL2 in M2 macrophages 4 h after irradiation. Similarly, PBM at 780 nm decreased mRNA expression levels of CCL3 and IL-6 by M1 macrophages 24 h after irradiation. Moreover, PBM at 780 nm increased the mRNA expression of TGFβ1 4 h after irradiation and decreased the expression of this gene after 24 h in M2 macrophages. Although red and infrared PBM were able to modulate and reduce M1/M2a-related markers, infrared laser irradiation promoted a temporal increase in the expression of TGFβ1 in M2 macrophages. Thus, depending on the time PBM is used on injured tissue, different parameters can promote optimal results by modulating specific macrophage phenotypes.

This article reports a case of oral mucosa lesions as the sole manifestation in Langerhans cell histiocytosis (LCH). This is a very uncommon manifestation of LCH since this disease preferably affects the bones with frequent involvement of the jaws. LCH may also involve other organs, particularly the lungs, liver, lymph nodes, and skin. The highlights of this report are the differential diagnosis, immunohistochemical analysis and, mostly, the therapeutic approach.

Background Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer and its occurrence in the oral cavity as a metastatic neoplasm is a rare event. We describe a fatal case of HCC with oral metastasis in a patient firstly diagnosed with prostatic and hepatic carcinomas. The histopathological examination revealed a hepatocyte-like tumour cells arranged in organoid structures as well as positivity to cytokeratin 8 and Hep Par 1. The present findings highlight the importance of a complete medical evaluation of the patient to identify possible oral repercussions of primary diseases.

Background Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and is successfully treated by surgery and radiation. However, some patients have recurrent tumours and in these cases, few treatments options are available. Cancer stem cells (CSC) have been observed and isolated from different solid tumours based on the expression of stem cell markers. These cells are associated with tumour initiation, progression as well as treatment resistance. In this study, the expression of stem cell markers CD44, Bmi1, Oct4 and Nanog was evaluated in non-neoplastic salivary tissue and in MEC. Methods Twenty-eight samples of MEC and their corresponding non-neoplastic salivary tissue were examined by immunohistochemistry and the stem cell markers expression was correlated with histological and clinical parameters. Results CD44 was expressed in the membrane of serous and mucous acini as well as in the ductal cells in normal gland tissue. Bmi1, Oct4 and Nanog were mainly expressed in ductal structures. In MEC, CD44 and Bmi1 showed strong expression in all types of neoplastic cells and both markers revealed intense expression in tumour invasive front. Oct4 and Nanog protein expression was associated with desmoplasia and perineural invasion. Only Oct4 positive tumours were associated with dissociative growth pattern and committed margins. Conclusion The stem cell markers CD44, Bmi1, Oct4 and Nanog are frequently expressed in MEC in relation to normal salivary gland and Oct4 and Nanog expression may contribute to aggressiveness and worst prognosis in MEC patients.

This study analyzed the effects of light-emitting diode (LED) therapy on the morphology of muscle tissue as well as collagen remodeling and matrix metalloproteinase 2 (MMP-2) activity in the skeletal muscle of rats following acute injury. Wistar rats were divided into four groups: (1) control, (2) sham, (3) untreated cryoinjury, and (4) cryoinjury treated with LED. Cryoinjury was induced by two applications of a metal probe cooled in liquid nitrogen directly onto the belly of the tibialis anterior muscle. For treatment, the LED equipment (wavelength 850 nm, output power 30 mW, and total energy 3.2 J) was used daily. The study periods were 1, 3, and 7 days after cryoinjury. Morphological aspects were evaluated through hematoxylin-eosin staining. The amount of collagen fibers was evaluated using Picro Sirius Red staining under polarized light. The gelatinase activity of MMP-2 was evaluated using zymography. The results showed significant reductions in inflammatory infiltrate after 3 days and an increased number of immature muscle fibers after 7 days. Furthermore, treatment induced a reduction in the gelatinolytic activity of MMP-2 after 1, 3, and 7 days in comparison to the untreated injury groups and increased the collagen deposition after 3 and 7 days in the treated groups. LED therapy at 850 nm induced a significant reduction in inflammation, decreased MMP-2 activity, and increased the amount of immature muscle and collagen fibers during the muscle repair process following acute injury.

Proliferative verrucous leukoplakia (PVL) is an aggressive form of oral leukoplakia that has a high morbidity and is more common in a woman with no smoking habit. A 68-year-old Caucasian male patient presented with a history of use of a removable dental prosthesis and reported to be a heavy smoker for the last 53 years, with a recent interruption of alcohol and other drug abuse. Clinical examination revealed a widespread leukoplakia lesion with 4 major intra-oral sites at the upper superior alveolar ridge and palate. Two sites were characterized as a homogeneous plaque, and 2 presented an exophytic verrucous surface. The first biopsy revealed hyperkeratosis and papillomatosis. The patient was referred to laser surgery treatment. Histologic findings revealed hyperkeratosis and papillomatosis, but now 1 of the sites revealed mild dysplasia. The final diagnosis was PVL, and the patient is still in follow-up, with no signs of new lesions 3 months after surgical intervention.

Oral squamous cell carcinoma is the most common malignant neoplasm of the oral cavity and is characterized by low survival rate and adverse prognosis. Objective: This study aimed to summarize accurately the scientific information about immunohistochemical markers related to prognosis and survival in patients with oral squamous cell carcinoma, due to the lack of one specific marker considered to be reliable to predict the behavior of this disease. Study Design: Articles written in English and published between 2007-2017 were chosen from PubMed, Scopus, Web of Science, LILACS, and LIVIVO databases. Results: A total of 2972 articles were found. After inclusion and exclusion criteria, 362 articles were followed for qualitative analysis and risk of bias definition of each article. One hundred twenty-eight articles with a high risk of bias were found; 90 had a moderate risk of bias and 144 had a low risk of bias. These 144 articles described 148 immunohistochemical markers for prognosis and survival. Among these markers, E-cadherin, Ki-67, β-catenin and CA9 were the most studied markers in at least 3 articles. Conclusion: These results suggest that these 4 proteins should be considered for future follow-up studies evaluating biological markers of prognosis and survival in patients with oral squamous cell carcinoma.

Objective: This study investigated components of the HH pathway (SHH, GLI1, and cyclin D1) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. Material and Methods: Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. Results: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared to the other proteins (P

A 57-year-old white female patient complaining of a 5-day painless smooth and pedunculated nodule covered by healthy oral mucosa at the lingual retromolar region was submitted to excisional biopsy. The differential clinical diagnoses comprised fibroma and fibrous hyperplasia. Histologic aspect revealed a benign neoplasia characterized by proliferation of mature adipocytes and spindle cells. These cells presented elongated nuclei and were arranged in small blocks through the fibrous connective tissue. The final diagnosis was pleomorphic lipoma. Oral lipoma is an uncommon mesenchymal neoplasia that usually affects the buccal mucosa and has a benign course without recurrence. The pleomorphic variant is a remarkably rare form of lipoma in oral mucosa, and most of these lesions were described in the tongue. The fusiform component of this lesion is similar to other lesions, requiring special attention at morphologic examination to exclude well-differentiated liposarcoma or immunohistochemical staining (CD34 e S100) to exclude other spindle cell lesions.

A 35-year-old black man complaining of chronic pain and redness of both lips presented, at oral examination, erosion and desquamation of lip vermilion and the commissures were fissured. From the clinical hypothesis of cheilitis glandularis, a biopsy of minor salivary gland was taken. The histologic examination revealed fragments of accessory salivary gland showing infiltration by mononuclear inflammatory cells at the connective tissue, and variable degrees of duct ectasia, resulting in chronic sialoadenitis. This finding confirmed the clinical diagnose and the patient started the treatment with intralesional steroid application with symptoms relief. Cheilitis glandularis is an uncommon chronic inflammatory disease of the lip minor salivary glands, especially in both lips, and presents a non-specific and challenging treatment. Cheilitis glandularis is not a life-threatening condition, but may affect the quality of life of the affected patients due to constant lip desquamation that can be symptomatic and can affect social interaction.

Myoepithelioma is a rare benign neoplasm representing 1.5% of all salivary gland tumors. Composed mainly by cells with myoepithelial differentiation, it affects most commonly parotid glands and middle-aged adults. A 20 year-old male patient presented with a progressive submucosal nodule in his left buccal mucosa with a 1-year duration. Asymptomatic, perceived more on palpation than through inspection, the lesion showed rubbery consistency, smooth surface, encapsulated aspect, and 2-cm diameter. A benign neoplasm was the main hypothesis, and a differential diagnosis composed of pleomorphic adenoma, neurilemoma, and leiomyoma suggested a biopsy procedure should be performed. Because the nodule presented entirely encapsulated during surgical intervention, it was completely removed and submitted to histologic analysis. Microscopic characteristics were consistent with a final diagnosis of myoepithelioma. The patient recovered without complications and showed no relapse after 1-year follow-up. This report aimed to present a case of a rare salivary gland neoplasm in unusual location and age range.

Objective This study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. Material and methods 12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. Results Associations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). Conclusion Macrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.