Publications by authors named "Elena Riet Correa Rivero"

47 Publications

Evaluation of two classification systems for oral epithelial dysplasia.

Oral Dis 2021 Apr 4. Epub 2021 Apr 4.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianopolis, Brazil.

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http://dx.doi.org/10.1111/odi.13867DOI Listing
April 2021

Prevalence of oral mucosal lesions in patients with pemphigus vulgaris: A systematic review and meta-analysis.

J Oral Pathol Med 2021 Mar 13. Epub 2021 Mar 13.

Department of Morphological Sciences, Biological Sciences Center, Federal University of Santa Catarina, Florianopolis, Brazil.

Objective: To assess the prevalence of oral mucosal lesions in patients with Pemphigus Vulgaris.

Methods: Observational studies reporting the prevalence of oral lesions in pemphigus vulgaris patients, without restriction to language and year of publication, were selected in a two-phase process. Search strategies were applied to PubMed, Scopus, Livivo, Web of Science, LILACS, Google Scholar, and OpenGrey databases. Articles assessing the prevalence of oral lesions in patients with conditions other than pemphigus vulgaris were excluded. Risk of bias analysis was performed using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated by the software R Statistics version 4.0.2 (The R Foundation). Confidence in cumulative evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.

Results: From 1957 studies identified, 40 were included in qualitative synthesis and 38 in meta-analyses. The pooled prevalence of patients with oral lesions solely or concurrent with other mucocutaneous lesions was 90.3%. The prevalence of patients with exclusive oral mucosal lesions was 50.8%. Risk of bias was considered low, and the certainty of evidence was very low.

Conclusion: Oral lesions were present in approximately nine out of 10 patients with pemphigus vulgaris. The oral mucosa was the most common site of disease onset. Further longitudinal studies are urged to assess the prevalence of oral lesions at different disease stages.
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http://dx.doi.org/10.1111/jop.13167DOI Listing
March 2021

Prognostic biomarkers for malignant transformation of oral potentially malignant disorders: a scoping review protocol.

JBI Evid Synth 2020 06;18(6):1349-1357

Department of Pathology, Federal University of Santa Catarina, Florianópolis, Brazil.

Objective: This scoping review aims to identify and systematically map the available evidence concerning the prognostic biomarkers for malignant transformation of oral potentially malignant disorders (OPMDs), and to identify and analyze possible knowledge gaps in this field of literature.

Introduction: It is hypothesized that diagnosis and treatment of oral cancer in its early stages may be the key to improving the prognosis and reducing treatment-related consequences. Oral potentially malignant disorders represent tissue alterations with a higher risk of malignant transformation compared to the normal mucosa. Therefore, the study of prognostic biomarkers for OPMD could represent new diagnosis and therapeutic targets and, consequently, contribute to the reduction of oral cancer burden worldwide.

Inclusion Criteria: Longitudinal studies investigating prognostic biomarkers regarding the malignant transformation of OPMD will be included. The initial OPMD diagnosis and the malignant transformation must have been confirmed by histopathological analysis. To achieve minimal heterogeneity, studies that assess biomarkers in other locations (blood, plasma or others) will be excluded.

Methods: Five electronic databases and three grey literature databases will be consulted. No restrictions regarding publication date will be applied. Only studies published in the Latin (Roman) alphabet, which comprises most of the European languages, will be included. Study selection will be performed by two authors in a two-phase process; if any disagreement arises, a third author will be consulted to make a final decision. Data extraction will be performed by two authors using a standardized extraction tool. The results will be described in details accordantly with the aims of this scoping review.
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http://dx.doi.org/10.11124/JBISRIR-D-19-00259DOI Listing
June 2020

Oral potentially malignant disorders: A scoping review of prognostic biomarkers.

Crit Rev Oncol Hematol 2020 Sep 16;153:102986. Epub 2020 May 16.

Department of Pathology, Federal University of Santa Catarina - Florianópolis, Brazil. Electronic address:

This scoping review aimed to map evidence regarding biomarkers for malignant transformation of oral potentially malignant disorders (OPMD). Seventy-three longitudinal studies investigating prognostic biomarkers for OPMD malignant transformation were included, encompassing 5612 disorders and 108 biomarkers, of which 72 were investigated by immunohistochemistry. Most biomarkers were assessed in one or two studies, while five (p53, Ki-67, podoplanin, p16, and DNA ploidy) were analyzed in five or more studies. All studies investigating podoplanin (n = 8) reported a significant association between positive/high immunoexpression and malignant transformation. Similarly, all studies assessing DNA ploidy (n = 5) found that aneuploidy or gross genomic aberrations were significantly associated with malignant transformation. Included studies often presented mixed data from different OPMD subtypes, inadequate description of population characteristics, and lack of adjusted analysis for confounding factors. One hundred and eight biomarkers were identified and, from these, podoplanin immunoexpression and DNA ploidy were considered promising candidates for future long-term clinical research.
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http://dx.doi.org/10.1016/j.critrevonc.2020.102986DOI Listing
September 2020

Prevalence of mucoepidermoid carcinoma among intraoral minor salivary gland tumors: A systematic review and meta-analysis.

J Oral Pathol Med 2020 Sep 4;49(8):720-726. Epub 2020 Jul 4.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, Brazil.

This study aimed to synthetize and critically appraise available evidence regarding mucoepidermoid carcinoma (MEC) prevalence among intraoral minor salivary gland tumors (MiSGT). Five main electronic databases and three grey literature databases were searched. The risk of bias (RoB) was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Proportion meta-analyses were performed. From 1321 studies identified, 82 were included in qualitative synthesis and 80 in meta-analyses. Sixteen were classified as high, 33 as moderate, and 33 as low RoB. A total of 12 774 MiSGT were found, of which overall MEC prevalence was 16.5% (95% Confidence Interval [95% CI] = 14.8%-18.4%). Most MiSGT were found in the palate (n = 7115), although MEC pooled prevalence in this anatomic location was only 13.6% (95% CI = 11.7%-15.6%). The retromolar area presented the highest pooled prevalence (58.9%; 95% CI = 47.0%-70.3%), followed by gingiva (28.8%; 95% CI = 22.7%-35.4%) and tongue (27.2%; 95% CI = 21.2%-33.6%). Regarding geographic location, Middle East presented the highest pooled prevalence (20.8%; 95% CI = 14.8%-27.6%), followed by America (20.0%, 95% CI = 17.2%-23%) and Europe (15.6%; 95% CI = 9.2%-23.5%). Among MiSGT, the MEC overall prevalence was approximately 16.5%. Although most MiSGT were found in the palate, the retromolar area was proportionally more affected by MEC.
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http://dx.doi.org/10.1111/jop.13073DOI Listing
September 2020

Prognostic and clinicopathological significance of podoplanin immunoexpression in oral and oropharyngeal squamous cell carcinoma: A systematic review.

J Oral Pathol Med 2021 Jan 23;50(1):1-9. Epub 2020 Jun 23.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, Brazil.

Background: Podoplanin (PDPN) is a glycoprotein associated with epithelial-mesenchymal transition, invasion, and metastasis in several types of malignancies, including oral and oropharyngeal squamous cell carcinoma (OSCC). The aim of this systematic review (SR) was to summarize and critically appraise the available evidence about the association between PDPN immunoexpression and clinicopathological features and its utility as a prognostic marker in OSCC.

Methods: Five electronic databases and three gray literature databases were searched for immunohistochemical studies, which were selected in a two-phase process.

Results: From 721 records identified, 22 cohort and seven analytical cross-sectional studies were included. Few studies reported that PDPN expression was associated with poorer survival rates in OSCC: overall survival = 4/12, disease-free survival = 4/7, and cancer-specific survival = 2/4 studies. Positive associations were most frequently reported on lymph node involvement, higher histopathological grade, and advanced clinical stages.

Conclusion: Within limitations of this SR, PDPN may be associated with lymph node involvement, histopathological grade, and clinical stage of OSCC. Current evidence suggests that PDPN could be a useful prognostic marker for OSCC that needs further exploration.
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http://dx.doi.org/10.1111/jop.13041DOI Listing
January 2021

Dystrophic calcification and respiratory metaplasia in the epithelial lining of odontogenic cysts: a study of 362 odontogenic cysts in a Brazilian population and literature review.

Pathol Res Pract 2020 Jun 18;216(6):152975. Epub 2020 Apr 18.

Department of Pathology, Federal University of Santa Catarina (UFSC), Florianopolis, Santa Catarina, Brazil. Electronic address:

Purpose: Main study: undertake a histological study of odontogenic cysts (OC) to determine the prevalence of dystrophic calcification and metaplasia to respiratory epithelium on a Brazilian population.

Literature Review: to review the literature for studies that investigated the prevalence of respiratory metaplasia and dystrophic calcification on OC.

Methods: Main study: a retrospective histopathological evaluation was made of the archives from a pathology laboratory. A total of 362 cases diagnosed as OC were identified; they were analyzed by two expert observers to determine the presence of dystrophic calcification and respiratory metaplasia. The association with sex, age and anatomic location was performed through statistical analysis.

Literature Review: a critical literature review was undertaken. Two main electronic databases (PubMed and LILACS) were searched. Retrospective studies of histological evaluation that determined the prevalence of epithelial metaplasia and dystrophic calcification on OC, with at least 10 cases, were included; their findings were summarized and discussed.

Results: Main study: the histological evaluation of OC revealed the presence of respiratory epithelium in 25 cases (6.9%) and dystrophic calcification in 24 cases (6.6%). Positive association was found to dystrophic calcification on residual cyst and age; respiratory metaplasia on OC and sex; respiratory metaplasia on residual cyst and gnatic bone; respiratory metaplasia in OC and gnatic bone; dystrophic calcification in OC and anatomic site of mandible.

Literature Review: eleven studies were included in the literature review, and respiratory metaplasia ranged from 0.0% to 19.2% while dystrophic calcification ranged from 2.5% to 40.5%.

Conclusions: the histological evaluation of this study found 6.9% of prevalence of respiratory metaplasia and 6.6% of dystrophic calcification, which is in accordance with the literature reviewed. Therefore, these phenomena must be taken into account in routine diagnosis services.
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http://dx.doi.org/10.1016/j.prp.2020.152975DOI Listing
June 2020

Cell-block as ancillary tool for the diagnosis of cystic and cyst-like jaw lesions.

Diagn Cytopathol 2020 Aug 29;48(8):717-723. Epub 2020 Feb 29.

Department of Pathology, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.

Background: The cell-block technique is a cytological diagnostic method that decreases cellular dispersion; however, its usefulness regarding intraosseous lesions is underexplored. Therefore, this study aimed to assess the diagnostic usefulness of cell-block for cystic and cyst-like jaw lesions.

Methods: Individuals with cystic or cyst-like jaw lesions who underwent aspiration biopsy were considered eligible. Aspiration of luminal content was prepared and processed by the cell-block technique. Cytological evaluations were blindly performed by two trained PhD students (in a single evaluation) and one oral and maxillofacial pathologist (OMP). Cohen's kappa statistic was used to measure inter-rater agreement.

Results: The sample was composed of 52 lesions, represented by 25 radicular cysts (RC), 17 odontogenic keratocysts (OKC), 5 idiopathic bone cavities (IBC), and 5 unicystic ameloblastomas (UA). The kappa coefficient of cell-block compared to histopathological diagnosis was 0.390 (95% confidence interval [95%CI], 0.195-0.585) for PhD students and 0.612 (95%CI, 0.433-0.791) for the OMP. The highest concordance rates between cell-block and histopathological diagnosis were observed for RC (PhD = 76.0%; OMP = 80.0%) and OKC (PhD = 58.8%; OMP = 76.5%). Conflicting results were found regarding IBC (PhD = 40.0%; OMP = 80.0%) and UA, that presented the overall lowest concordance rates (PhD = 20.0%; OMP = 40.0%).

Conclusion: The cell-block technique presented a high diagnostic usefulness for detecting RC and OKC and, if associated with clinical and radiographic characteristics, might be sufficient for final diagnosis of these diseases. Regarding IBC and UA, an analysis with a higher number of cases is recommended to determine the true usefulness of the cell-block as ancillary tool for the diagnosis of these lesions.
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http://dx.doi.org/10.1002/dc.24400DOI Listing
August 2020

A Brazilian multicentre study of 2,497 isolated cases of odontogenic keratocysts.

Oral Dis 2020 Apr 14;26(3):711-715. Epub 2020 Feb 14.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men.
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http://dx.doi.org/10.1111/odi.13278DOI Listing
April 2020

Prognostic biomarkers for malignant transformation of oral potentially malignant disorders: a scoping review protocol.

JBI Database System Rev Implement Rep 2020 Jan 6. Epub 2020 Jan 6.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, Brazil.

Objective: This scoping review aims to identify and systematically map the available evidence concerning the prognostic biomarkers for malignant transformation of oral potentially malignant disorders (OPMD), and to identify and analyze possible knowledge gaps in this field of literature.

Introduction: It is hypothesized that diagnosis and treatment of oral cancer in its early stages may be the key to improving the prognosis and reducing treatment-related consequences. OPMD represent tissue alterations with a higher risk of malignant transformation compared to the normal mucosa. Therefore, the study of prognostic biomarkers for OPMD could potentially represent new diagnosis and therapeutic targets and, consequently, contribute to the reduction of oral cancer burden worldwide.

Inclusion Criteria: Longitudinal studies investigating prognostic biomarkers regarding the malignant transformation of OPMD will be included. The initial OPMD diagnosis and the malignant transformation must have been confirmed by histopathological analysis. Studies that aim to achieve minimal homogeneity, or that assess biomarkers in other locations (blood, plasma or others) will be excluded.

Methods: Five electronic databases and three grey literature databases will be consulted. No restrictions regarding publication date will be applied. Only studies published in the Latin (Roman) alphabet, which comprises most of the European languages, will be included. Study selection will be performed by two authors in a two-phase process; if any disagreement arises, a third author will be consulted to make a final decision. Data extraction will be performed by two authors using a standardized extraction tool. The results will be described in details accordantly with the aims of this scoping review.
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http://dx.doi.org/10.11124/JBISRIR-D-19-00259DOI Listing
January 2020

Comparative analysis between developmental and inflammatory odontogenic cysts: retrospective study and literature review.

Oral Maxillofac Surg 2020 Mar 19;24(1):73-84. Epub 2019 Dec 19.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil.

Purpose: To assess epidemiological, clinical, and radiographic characteristics of odontogenic cysts (OCs) in a South Brazilian sample and to compare the results with international literature.

Methods: For the main study purposes, biopsy and histopathological records were retrospectively analyzed from December 2006 to December 2018, OC cases were selected, and data about clinical characteristics were evaluated. Further, a literature review was performed for similar studies.

Results: In the main study, the prevalence of OCs was 11.26% (n = 406), the majority of patients was male (56.73%), and the mean age was 39 ± 17.33 years. Radicular cyst was the most common OC (46.06%), followed by the odontogenic keratocyst (15.02%), dentigerous cyst (14.04%), and paradental cyst (13.55%). Inflammatory OCs were more prevalent in the maxilla (54.84%) and developmental cysts in the mandible (69.92%) (p < 0.05). Individuals with inflammatory OCs were usually older (41.0 ± 15.34 years) than the ones with developmental OC (28.0 ± 19.68 years) (p < 0.05). Regarding the literature review, 22 articles were included. Analysis of pooled data showed that global prevalence of OCs was 11.62% (95%CI = 9.97-13.37), from which radicular cyst was the most common (54.26%; 95%CI = 49.30-59.18), followed by dentigerous cyst (22.94%; 95%CI = 19.22-26.89) and odontogenic keratocyst (11.99%; 95%CI = 8.88-15.49). Furthermore, studies from Asia (72.40%; 95%CI = 70.30-74.40) and South America (68.48%; 95%CI = 64.07-72.72) presented the highest frequencies of inflammatory OCs.

Conclusion: The main study showed that the prevalence of OCs was 11.26%, which corroborates with international literature. Considering geographic variability of OC distribution, public health authorities and researchers could use these data for the development of focused prevention interventions, especially with regard to inflammatory OCs.
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http://dx.doi.org/10.1007/s10006-019-00816-8DOI Listing
March 2020

Retrospective study of 124 cases of salivary gland tumors and literature review.

J Clin Exp Dent 2019 Nov 1;11(11):e1025-e1032. Epub 2019 Nov 1.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.

Background: Salivary gland tumors are a rare and morphologically diverse group of lesions and their frequency is still unknown in several parts of the world. The knowledge of its population characteristics contributes to a better understanding of its etiopathogenesis. Objectives: This study investigated the frequency of salivary gland tumors in a region of southern Brazil and compared these data in a literature review.

Material And Methods: A retrospective study was conducted of salivary gland tumors diagnosed at two pathology centers from 1995 to 2016. Patient age and gender, tumor site and frequency, histopathological diagnosis, and symptomatology were evaluated. Chi-squared tests were used to assess the associations between variables. To compare our data, we also conducted a literature review of publications in the PubMed and LILACS databases of retrospective studies of salivary gland tumors.

Results: A total of 124 salivary gland tumor cases was identified, 81 (65.3%) of which were classified as benign and 43 (34.6%) as malignant. Most tumors occurred in the parotid gland (57.2%). Pleomorphic adenoma was the most common tumor (59.6%), followed by adenocarcinoma not otherwise specified (8.8%). The tumors occurred more often in women (54.8%) than in men (45.2%). Malignant tumors were associated with pain in 31.4% of cases (<0.05). The literature review included 35 articles from different countries. Women were most affected, with a mean age of 41.7 years. The most common benign tumor was pleomorphic adenoma (48.2%) and the most common malignant tumor was mucoepidermoid carcinoma (8.7%).

Conclusions: The results of the present study showed that salivary gland tumors are rare. The parotid gland is the most common location and pleomorphic adenoma are the most frequent lesions. The malignant tumors presented as several histological types and the incidence was variable globally. Salivary gland neoplasms, salivary gland diseases, oral surgery, epidemiology.
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http://dx.doi.org/10.4317/jced.55685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825733PMC
November 2019

The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis.

Clin Oral Investig 2019 Jul 20;23(7):2849-2859. Epub 2019 May 20.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Objectives: This systematic review (SR) aimed to summarise and critically appraise available evidence about the association between the synergistic consumption of alcohol and tobacco and the occurrence of oral squamous cell carcinoma (OSCC).

Materials And Methods: Observational studies investigating the association between the synergistic consumption of alcohol and tobacco and OSCC occurrence were included. Studies were selected in a two-phase process and searches were conducted on five main electronic databases, complemented by three grey literature databases.

Results: From 3260 records identified, 33 articles were included for qualitative analysis, of which 15 were included in the meta-analyses. Overall, the synergistic consumption was positively associated with the occurrence of OSCC (odds ratio [OR] = 5.37; 95% confidence interval [95%CI] = 3.54-8.14). Increased odds for OSCC occurrence were observed regarding the synergistic consumption of alcohol and smoked tobacco (OR = 4.74; 95%CI = 3.51-6.40), alcohol and smokeless tobacco (OR = 7.78; 95%CI = 2.86-21.14), and alcohol, smoked tobacco, and smokeless tobacco (OR = 16.17; 95%CI = 7.97-32.79).

Conclusions: According to the results of this SR, the synergistic consumption of alcohol and tobacco (both smoked and smokeless) significantly increased the odds for the occurrence of OSCC.

Clinical Relevance: The knowledge provided by this SR may be useful for a better understanding of differences in the effect of synergistic consumption of alcohol and tobacco products in OSCC development. These data might aid healthcare authorities to develop measures for tobacco and alcohol control considering the needs of their population.
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http://dx.doi.org/10.1007/s00784-019-02958-1DOI Listing
July 2019

Prevalence of odontogenic cysts and tumors associated with impacted third molars: A systematic review and meta-analysis.

J Craniomaxillofac Surg 2019 Jun 30;47(6):996-1002. Epub 2019 Mar 30.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, Brazil. Electronic address:

Purpose: This systematic review aimed to investigate the prevalence of odontogenic cysts and tumors associated with impacted third molars (ITM).

Methods: Only studies that performed histopathological diagnosis of lesions were eligible for inclusion. Five main electronic and three grey literature databases were searched. Risk of bias (RoB) of included articles was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.

Results: From 1,300 studies identified, 16 met the inclusion criteria. Seven studies were classified as high, seven as moderate, and two as low RoB. The prevalence of odontogenic cysts and tumors associated with ITM was 5.3% (95%CI: 3.1%-8.1%) of ITM. Odontogenic cysts in particular were found in 4.4% (95%CI: 2.5-6.8%) of the extracted ITM, whilst odontogenic tumors in 0.5% (95%CI: 0.2-0.9%). The dentigerous cyst was mentioned in eleven studies with a pooled prevalence of 2.1% (95%CI: 1.4-3.1%). The odontogenic keratocyst was cited by nine studies and had a prevalence of 0.5% (95%CI: 0.2-0.7%). The radicular cyst was mentioned only in three articles and the pooled prevalence was 4.7% (95%CI: 0.0-19.4%) CONCLUSION: Odontogenic cysts and tumors were found in 5.3% of ITM extracted. The most common lesions were the radicular cyst, dentigerous cyst, and odontogenic keratocyst.
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http://dx.doi.org/10.1016/j.jcms.2019.03.026DOI Listing
June 2019

Fibrous dysplasia with secondary aneurysmal bone cyst-a rare case report and literature review.

Oral Maxillofac Surg 2019 Mar 13;23(1):101-107. Epub 2019 Feb 13.

Department of Pathology, Center of Health Sciences, Federal University of Santa Catarina, University Campus, Trindade, Florianópolis, 88.040-370, Santa Catarina, Brazil.

Introduction: Fibrous dysplasia (FD) and aneurysmal bone cyst (ABC) are uncommon non-neoplastic intraosseous lesions, and the occurrence of concomitant FD and ABC is extremely rare.

Case Report: An 11-year-old boy presented with gradual progressive enlargement of his right zygomatic bone over 4 years prior to presentation. Computed tomography revealed a lesion with a central bony area showing a ground-glass appearance surrounded by a well-defined expansile lesion with internal septations. An incisional biopsy was performed and suggested a fibro-osseous lesion. Resection was performed, followed by immediate reconstruction using autogenous bone graft from the iliac crest. Histopathological examination revealed irregularly shaped trabeculae comprising immature woven bone in a fibroblastic cell-rich stroma. Blood-filled sinusoidal spaces lined by fibrous septa containing scattered multinucleated giant cells were observed peripherally. These findings were compatible with concomitant FD and ABC. The patient was disease-free at the time of his 10-month follow-up.

Conclusions: Based on our literature search, this report is the first to describe concomitant monostotic FD and ABC in the zygomatic bone. Accurate diagnosis requires careful investigation and examination of clinical, radiographical, and histopathological features. The treatment of choice should provide an esthetic and functional improvement in the patient.
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http://dx.doi.org/10.1007/s10006-019-00741-wDOI Listing
March 2019

Actinic cheilitis and lip squamous cell carcinoma: Literature review and new data from Brazil.

J Clin Exp Dent 2019 Jan 1;11(1):e62-e69. Epub 2019 Jan 1.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Background: To investigate the prevalence of malignant and potentially malignant lesions of the lip in an oral pathology service and to compare these data with a literature review.

Material And Methods: A total of 3173 biopsy reports and histopathological records were analyzed. Cases with a histological diagnosis of actinic cheilitis (AC) with or without epithelial dysplasia, in situ carcinoma, or lip squamous cell carcinoma (LSCC) were included. A comprehensive literature review was conducted to investigate the prevalence of AC and/or LSCC.

Results: 124 cases (3.91%) were included, 75 (60.5%) had some degree of epithelial dysplasia and 31 (25.0%) were LSCC. Clinically, most of the lesions were diagnosed as AC (50.8%); however, eight cases clinically reported as AC were histologically diagnosed as LSCC. Regarding clinical characteristics, most individuals were fair-skinned male, with mean age of 54.3±12.3 years, and with a history of long-term solar exposure. Furthermore, 18 articles were selected from the literature, showing that the lower lip was predominantly affected and that most individuals were males, fair-skinned, and older than 40 years.

Conclusions: Since most of the cases diagnosed clinically as AC presented some degree of epithelial dysplasia, it is important to emphasize the value of biopsy and the histological evaluation of this lesion. Actinic cheilitis, Precancerous conditions, In situ carcinoma, Oral diagnosis, Mouth neoplasms.
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http://dx.doi.org/10.4317/jced.55133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343992PMC
January 2019

Inhibition of cancer stem cells promoted by Pimozide.

Clin Exp Pharmacol Physiol 2019 02 28;46(2):116-125. Epub 2018 Nov 28.

Department of Morphological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in melanoma, central nervous system tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic, and hepatocellular carcinoma have been showed. Moreover, advantages as clinical use approved by the Food and Drug Administration (FDA), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents. The action mechanism remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial-to-mesenchymal transition (EMT), through inhibition of Wnt-β/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription (STAT-3 and 5), pathway which is activated and up-regulated in CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat-containing protein 48 (WDR48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state. Based on this perspective, the aim of this manuscript is to review the antineoplastic role of Pimozide during tumorigenesis and its potential to revert the process of undifferentiation and proliferation of CSC through different vias.
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http://dx.doi.org/10.1111/1440-1681.13049DOI Listing
February 2019

Immunohistochemical expression of RANKL in oral giant cell lesions is predictive of aggressiveness.

Braz Oral Res 2018 Oct 29;32:e115. Epub 2018 Oct 29.

Universidade Federal de Santa Catarina - UFSC, Department of Pathology, Florianópolis, Santa Catarina, Brazil.

The aim of this study was to evaluate the immunohistochemical expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and of osteoprotegerin (OPG), important proteins correlated with osteoclastogenesis, in central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) and to compare their expression with the histological and clinical parameters for quantification of multinucleated giant cells (MGC) and their nuclei, lesion size, and recurrences. Twenty cases of each lesion type were selected to quantify the number of MGCs and nuclei/mm2 of connective tissue. The immunoreactivity of RANKL and OPG was expressed as a percentage of the marked area in the stroma. Clinical data were collected from pathoanatomical and medical reports. No statistical differences were found for the number of MGCs (p = 0.24) between PGCL and CGCL, but the number of nuclei within the MGCs was higher in CGCL (p = 0.01). RANKL expression was higher in CGCL than in PGCL (p = 0.04) and all recurrent lesions showed higher RANKL and OPG expressions than nonrecurrent lesions. We report higher RANKL expression and a greater number of nuclei in CGCL, which may explain the difference in clinical behaviour between these lesions and their pathogenesis.
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http://dx.doi.org/10.1590/1807-3107bor-2018.vol32.0115DOI Listing
October 2018

Evaluation of cell proliferation in cystic lesions associated with impacted third molars.

Microsc Res Tech 2018 Nov 8;81(11):1241-1245. Epub 2018 Oct 8.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

The purpose of this study was to evaluate the metabolism and epithelial cell proliferation of odontogenic keratocyst (OKC), dentigerous cyst (DC), and unicystic ameloblastoma (UA) by quantifying the nucleolar organizing regions (AgNORs) and Ki-67 protein immunoexpression. Forty-eight cases (16 OKC, 16 DC, and 16 UA) were evaluated retrospectively. The metabolism and epithelial cell proliferation was measured by the Ki-67 positive cell percentage index and by the mean AgNOR count in each group. The Ki-67 and AgNOR counts were significantly higher in OKC comparing to the DC and UA (p < .001). Ki-67 positive cells were observed higher in suprabasal cell layers of OKC with uniform distribution, a few of them were predominantly observed in basal cell layer in DC and UA. The AgNOR count was significantly higher in the OKC basal cell layers and observed throughout the lining epithelium of DC and UA. Ki-67 and AgNOR reinforced the aggressive character of OKC, presenting high metabolism and cellular proliferation compared to DC and UA, possibly due to its more aggressive clinical behavior and high recurrence rate. RESEARCH HIGHLIGHTS: We evidence higher metabolism and epithelial cell proliferation in OKC when compared to UA and DC, supporting its aggressive aspect and its high rate of recurrence. OKC had intense and predominant labeling of Ki-67 on the suprabasal layer unlike UA and DC.
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http://dx.doi.org/10.1002/jemt.23128DOI Listing
November 2018

A multicentre study of oral paracoccidioidomycosis: Analysis of 320 cases and literature review.

Oral Dis 2018 Nov 6;24(8):1492-1502. Epub 2018 Aug 6.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Objectives: To investigate the frequency of oral paracoccidioidomycosis from representative geographical regions of Brazil and to compare the data with a literature review.

Materials And Methods: A retrospective study was conducted on 108,304 biopsies obtained from 1953 to 2016 at six Brazilian oral and maxillofacial pathology services. Demographic data and clinical and histopathological diagnosis of oral paracoccidioidomycosis were evaluated. A literature review of oral paracoccidioidomycosis studies published in three electronic databases was carried out. Data were analysed descriptively.

Results: A total of 320 cases of oral paracoccidioidomycosis were surveyed (0.3% of the oral lesions at the centres studied). The lesions were more frequent among male patients. The gingiva/alveolar ridge was the most affected site. Mean age of affected individuals was 51.3 years (±11.7). The literature review showed a higher incidence of oral paracoccidioidomycosis in the south-east and south regions of Brazil. Male individuals and individuals between 50 and 59 years were most affected.

Conclusions: Oral paracoccidioidomycosis is an uncommon lesion observed in oral biopsy samples. The differences in the relative frequency of oral paracoccidioidomycosis are related to geographical variations. Men between 50 and 59 years are more affected. This study provides helpful information for clinicians in the diagnosis of oral paracoccidioidomycosis.
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http://dx.doi.org/10.1111/odi.12925DOI Listing
November 2018

Maté consumption association with upper aerodigestive tract cancers: A systematic review and meta-analysis.

Oral Oncol 2018 07 11;82:37-47. Epub 2018 May 11.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina - Florianópolis, Santa Catarina, Brazil.

Maté is a beverage regularly consumed by Latin American populations. Upper aerodigestive tract (UADT) cancers are frequent in this region and are suspected to be associated with maté consumption. The aim of this systematic review and meta-analysis was to answer a focused question: "Is there an association between maté consumption and occurrence of the UADT cancer?". Studies investigating any association between maté consumption and occurrence of UADT cancer were included. Out of the 569 studies, 18 met the inclusion criteria for qualitative and 15 for quantitative analysis. An increased odds was observed regarding maté consumption and overall occurrence of UADT cancer (OR = 2.24; 95%CI = 1.74-2.87). Consistent evidence of a positive association was found for all UADT subsites, oral, pharynx, esophagus and larynx. No differences in effect were found between consumption of cold/warm and hot/very hot mate (OR = 1.08; 95%CI = 0.83-1.41). Consumption of more than one liter of maté per day was associated with increased odds of having UADT cancer compared to an intake of less than one liter per day (OR = 1.72; 95%CI = 1.47-2.01). According to published data, regardless of the temperature, maté consumption significantly increased the odds of occurrence of UADT cancer.
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http://dx.doi.org/10.1016/j.oraloncology.2018.04.023DOI Listing
July 2018

Prevalence of oral potentially malignant disorders: A systematic review and meta-analysis.

J Oral Pathol Med 2018 Aug 6;47(7):633-640. Epub 2018 Jun 6.

Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, Brazil.

Oral potentially malignant disorders (OPMD) are chronic conditions, which have a higher risk of transformation to oral squamous cell carcinoma. The aim of this systematic review and meta-analysis was to answer the question: "What is the prevalence of oral potentially malignant disorders among adults?" Studies reporting the prevalence of these conditions (leukoplakia, erythroplakia, oral submucous fibrosis [OSMF], and actinic cheilitis) were selected, only studies in which a clinical assessment and histopathological confirmation were performed were included. Of the 5513 studies, 22 met the inclusion criteria for qualitative and quantitative analyses. The risk of bias (RoB) of the selected studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Seven studies were classified as high risk, 12 as moderate risk, and 3 as low RoB. The meta-analysis showed that the prevalence of OPMD was 4.47% (95% CI = 2.43-7.08). The most prevalent OPMDs were OSMF (4.96%; 95% CI = 2.28-8.62) and leukoplakia (4.11%; 95% CI = 1.98-6.97). OPMDs were identified more commonly in males (59.99%; 95% CI = 41.27-77.30). Asian and South American/Caribbean populations had the highest prevalence rates of 10.54% (95% CI = 4.60-18.55) and 3.93% (95% CI = 2.43-5.77), respectively. The overall prevalence of OPMD worldwide was 4.47%, and males were more frequently affected by these disorders. The prevalence of OPMD differs between populations; therefore, further population-based studies may contribute to the better understanding of these differences.
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http://dx.doi.org/10.1111/jop.12726DOI Listing
August 2018

Incidence of reactive hyperplastic lesions in the oral cavity: a 10 year retrospective study in Santa Catarina, Brazil.

Braz J Otorhinolaryngol 2019 Jul - Aug;85(4):399-407. Epub 2018 Apr 17.

Universidade Federal de Santa Catarina (UFSC), Departamento de Patologia, Florianópolis, SC, Brazil.

Introduction: Reactive hyperplastic lesions develop in response to a chronic injury simulating an exuberant tissue repair response. They represent some of the most common oral lesions including inflammatory fibrous hyperplasia, oral pyogenic granuloma, giant cell fibroma, peripheral ossifying fibroma, and peripheral giant cell lesions.

Objective: The incidence of those lesions was investigated in an oral pathology service, and the clinical characteristics, associated etiological factors, concordance between the clinical and histopathological diagnostic was determined.

Methods: A total of 2400 patient records were screened from 2006 to 2016. Clinical features were recorded from biopsy reports and patients' files.

Results: A total of 534 cases of reactive hyperplastic lesions were retrieved and retrospectively studied, representing 22.25% of all diagnoses. The most frequent lesion was inflammatory fibrous hyperplasia (72.09%), followed by oral pyogenic granuloma (11.79%), giant cell fibroma (7.30%), peripheral ossifying fibroma (5.24%), and peripheral giant cell lesions (3.55%). Females were predominantly affected (74.19%), the gingiva and alveolar ridge were the predominant anatomical site (32.89%), and chronic traumatism was presented as the main etiological factor. The age widely ranges from the 1st decade of life to the 7th. Clinically, the reactive hyperplastic lesions consisted of small lesions (0.5-2cm) and shared a strong likeness in color to the oral mucosa. The concordance between the clinical and histopathological diagnostic was high (82.5%).

Conclusion: Reactive hyperplastic lesions had a high incidence among oral pathologies. The understanding of their clinical features helps to achieve a clearer clinical and etiological diagnosis, and the knowledge of factors related to their development. This may contribute to adequate treatment and positive prognosis.
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http://dx.doi.org/10.1016/j.bjorl.2018.03.006DOI Listing
September 2019

Intraoral Potentially Malignant Disorders in a Brazilian Oral Pathology Service: Epidemiological, Clinical, and Histopathological Findings.

J Oncol 2018 1;2018:2325808. Epub 2018 Mar 1.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.

The aim of this study was to investigate the characteristics of individuals with intraoral potentially malignant disorders (IOPMD) in an oral pathology service in Brazil. Cases were screened based on clinical diagnosis of leukoplakia (LKP), erythroleukoplakia (ELKP), and erythroplakia (EP). Clinical data and information regarding associated factors were gathered from biopsy reports. Histological diagnoses were collected from histopathological records. Among 208 IOPMD cases, 84.13% involved LKP; 11.1%, ELKP; and 4.8%, EP. The most affected sites were the gingiva and buccal mucosa. Histologically, epithelial dysplasia was present in 66.8% of the lesions, acanthosis and hyperkeratosis without epithelial dysplasia were present in 27.9%, and squamous cell carcinoma was present in 2.9%. Most patients were males, fair-skinned, with mean age of 53.4 years. Chronic smokers represented 73% of subjects, of which 30% also consumed alcohol. Smokers and drinkers were mostly males ( < 0.001). EP and ELKP represented histologically more severe degrees of epithelial dysplasia than LKP ( < 0.001). In conclusion, individuals with IOPMD were more frequently fair-skinned men in the sixth decade of life, with smoking habit. Special attention is required to clinical diagnoses of ELKP and EP since the prevalence of severe epithelial dysplasia, in situ carcinoma, and squamous cell carcinoma is higher than in LKP.
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http://dx.doi.org/10.1155/2018/2325808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852874PMC
March 2018

The risk of osteonecrosis on alveolar healing after tooth extraction and systemic administration of antiresorptive drugs in rodents: a systematic review.

J Craniomaxillofac Surg 2018 Feb 20;46(2):245-256. Epub 2017 Nov 20.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, 88.040.370, SC, Brazil. Electronic address:

Purpose: There is much concern about the increasing number of patients with medication-related osteonecrosis of the jaw (MRONJ), and many studies have been published in an attempt to understand the pathophysiology of this condition. This study aimed to systematically review the literature on MRONJ arising in rodents under antiresorptive drug therapy after tooth extraction.

Methods: A search of electronic databases, including LILACS, PROQUEST, PubMed, SCOPUS, and the Web of Science.

Results: The search resulted in 2319 titles after removing the duplicates, and one paper was identified using the reference list. Ninety-eight full-text papers were then screened for eligibility, resulting in 20 for inclusion in the final qualitative synthesis. The quality of the articles was assessed using the 'ARRIVE' tool.

Conclusion: Despite the wide heterogeneity of the methodologies used by the authors, the current available evidence suggests that the combination of bisphosphonate and/or denosumab therapy and tooth extraction is associated with osteonecrosis of the jaw in rodents.
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http://dx.doi.org/10.1016/j.jcms.2017.11.008DOI Listing
February 2018

A multicenter study of malignant oral and maxillofacial lesions in children and adolescents.

Oral Oncol 2017 12 5;75:39-45. Epub 2017 Nov 5.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address:

Objectives: To investigate the frequency of malignant oral and maxillofacial lesions among children and adolescents from representative geographic regions of Brazil.

Materials And Methods: A retrospective study was conducted on biopsies obtained from 1990 to 2016 at six Brazilian oral and maxillofacial pathology referral centers. A total of 85,105 biopsy specimens from children and adolescents were analyzed. Gender, age, anatomical location, symptomatology and histopathological diagnosis were evaluated. Data were analyzed using descriptive statistical methods.

Results: Fifty-eight (0.06%) malignant oral and maxillofacial lesions were diagnosed in children (19%) and adolescents (81%). The lesions were more frequent among females (60.3%) and adolescents. The most prevalent lesions were mucoepidermoid carcinomas (22.4%), osteosarcomas (13.8%), squamous cell carcinomas (12.1%), and Burkitt's lymphomas (12.1%). The most commonly affected sites were the palate (19%), mandible (13.8%), and maxilla (13.8%). Almost half the patients were asymptomatic.

Conclusion: Pediatric oral and maxillofacial malignant lesions were infrequent and showed wide diversity, with a prevalence of mucoepidermoid carcinomas. Analysis of malignant lesions in children and adolescents helps pediatric dentists and oncologists to obtain a better understanding of such lesions and to reduce the time for diagnosis, with a consequent improvement of prognosis.
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http://dx.doi.org/10.1016/j.oraloncology.2017.10.016DOI Listing
December 2017

Evaluation of Mandibular Bone After Dental Extraction in Rats Treated With Antiresorptive Drugs.

J Oral Maxillofac Surg 2018 03 3;76(3):474-482. Epub 2017 Aug 3.

Associate Professor, Department of Pathology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Electronic address:

Purpose: Zoledronic acid (ZOL) and denosumab (Dmab) are commonly used to treat bone pathologies. Because these drugs suppress bone metabolism, this study sought to compare their effect on bone repair after tooth extraction.

Materials And Methods: Four-week-old male Wistar rats were randomly assigned to 1 of 3 groups: ZOL 0.125 mg/kg, Dmab 0.25 mg/kg, or saline solution 10 mL/kg (control). After 1 week of treatment, the first left molar was extracted; the rats were euthanized at 28 days. The jaws were removed and photographed for macroscopic analysis of wound healing and then subjected to tomographic and histologic analyses. Immunohistochemistry was carried out against the receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG).

Results: No difference in wound healing, presence of inflammatory infiltrate and bone sequestration, or osteocyte expression of RANKL and OPG was found among groups. Tomographic analysis showed that the ZOL group had less alveolar resorption and more complete alveolar repair compared with the other groups. There was a statistically significant difference in the OPG marker in the control (P = .008) and ZOL (P = .05) groups when comparing the extracted and non-extracted sides.

Conclusion: Systemic use of ZOL can improve alveolar bone healing; however, the potential risk for the development of osteonecrosis should be considered. Higher expression of OPG seems to be associated with the control of osteoclastogenesis during bone repair.
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http://dx.doi.org/10.1016/j.joms.2017.07.172DOI Listing
March 2018

Tissue integrity, costs and time associated with different agents for histological bone preparation.

Microsc Res Tech 2017 Apr 6;80(4):344-349. Epub 2016 Nov 6.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

The selection of an appropriate demineralizing solution in pathology laboratories depends on several factors such as the preservation of cellularity, urgency of diagnostic and financial costs. The aim of this study was to test different decalcification bone procedures in order to establish the best value of these in formalin-fixed and paraffin-embedded samples. Femurs were removed from 13 adult male Wistar rats to obtain 130 bone disks randomly divided into five groups that were demineralized in different concentrations of nitric acid (Group I); formic acid (Group II); acetic acid (Group III); EDTA, pH7.4 (Group IV) and Morsés solution (Group V). Serial, 3-μm-thick sections were obtained and stained with hematoxylin-eosin to calculate the percentage of osteocyte-occupied lacunae. The sections were also stained with Masson's trichrome in conjunction with picrosirius red under polarized light followed by a semi-quantitative analysis to verify the adjacent muscle-to-bone integrity and preservation of collagen fibres. The highest percentage of osteocyte-occupied lacunae was found with 10% acetic acid solution (95.64 ± 0.95%) and Group I (nitric acid) demanded the shorter time (0.8-5.7days). Of all solutions, 5% nitric acid incurred the lowest cost to achieve complete demineralization compared with other solutions (p < .001). Group IV (EDTA) had the highest integrity of muscle and collagen type I and III (P < 0.01). Demineralization with 10% acetic acid was the most effective at preserving bone tissue, while 5% EDTA was the best at maintaining collagen and adjacent muscle to bone. In conclusion, nitric acid at 5% showed the most efficient result as it balanced both time and cost as a demineralizing solution.
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http://dx.doi.org/10.1002/jemt.22798DOI Listing
April 2017

Aspiration and cytological evaluation of idiopathic bone cavities of the jaw.

Tissue Cell 2017 Jun 20;49(3):435-439. Epub 2017 Mar 20.

Department of Pathology, Federal University of Santa Catarina, Florianópolis, SC, Brazil.

The idiopathic bone cavity (IBC) is an intraosseous pseudocyst devoid of epithelial lining. Clinically, IBCs of the jaw are asymptomatic and normally found in routine radiographic exams. Although the literature regarding the content of IBCs is controversial, the final diagnosis is usually aided by the discovery of an empty cavity upon surgical exploration. The aim of this study was to perform cytological and histological analysis of IBC contents. Cytological analysis of nine cases of IBC was performed after puncture and processed by the cell block technique. Histological analysis was performed in six cases in which it was possible to collect enough material by curettage of bone walls. Remarkably, cell block analysis revealed the presence of fibrin, often arranged as a net; erythrocytes; and inflammatory cells, with a predominance of lymphocytes as well as some macrophages and neutrophils. Histological analysis showed the presence of scant connective tissue, bone trabeculae, hemorrhagic foci, and hemosiderin. Only two cases presented scattered multinucleated giant cells. Cytological evaluation of IBC content by the cell block technique might represent a useful diagnostic tool, especially in cases in which there is no available material for curettage in the cavity.
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http://dx.doi.org/10.1016/j.tice.2017.03.005DOI Listing
June 2017

The Role of the Complex USP1/WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells.

Curr Stem Cell Res Ther 2017 ;12(5):416-422

Department of Pathology, Federal University of Santa Catarina, Reitor Joao David Ferreira Lima Campus, Zip Code 88040-900, Florianopolis, Santa Catarina. Brazil.

Background: Recently, some studies identified the Basic-Helix-Loop-Helix (bHLH) transcription factor as a significant regulator for the evolution of neoplasms. The binding between bHLH proteins and DNA is restricted by heterodimerization with Inhibitors of DNA binding (ID). IDs prevent cellular differentiation, promote growth and sustain tumor development. The wide presence of stem cells in cancers suggests that genes ID are essential to cancer stem cells (CSC) progress. The enzyme Ubiquitin-specific protease 1 (USP1) is reported to deubiquitinate and stabilize IDs. Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics. USP1 has its activity potentiated when bound to protein WD repeat-containing protein (WDR48).

Objective: To identify the influence of the complex USP1/WDR48 during the CSC tumorigenesis process, and whether this complex is a possible therapeutic target.

Methods: A literature search regarding the role of the complex USP1/WDR48 in inhibiting differentiation and increasing proliferation of CSC was performed, and possible selective molecule inhibitors of these deubiquitinase proteins were investigated.

Results: There is evidence that USP1/WDR48 complex promotes stem cell conservation and regulation of DNA damage repair. For this reason, inhibitors as Pimozide, GW7647, C527, SJB2-043, ML323 have been studied to inhibit USPs in cases of treatment intervention.

Conclusion: It is consolidated in the literature the role of USP1/WDR48 during tumorigenesis. However, these studies are not enough to completely clarify the process; but certainly, the researchers are converging towards a promising direction to provide a new treatment option for cancer.
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http://dx.doi.org/10.2174/1574888X12666170315104013DOI Listing
April 2018