Abstract Emerging evidence has revealed a cross-talk in the etiopathogenesis of burning mouth syndrome (BMS) related to peripheral nerve fibers (NF) and neuropeptides secreted by mast cells. Here, we investigated the S-100+ density and PGP 9.5+ integrity of peripheral NF and the tryptase+ mast cell density in the oral mucosa of BMS patients and healthy individuals. A total of 23 oral mucosa specimens (12 BMS and 11 controls) were evaluated. The clinical diagnosis of BMS was based on a careful examination, excluding other local and systemic causes. Samples were taken from an incisional biopsy of the tongue mucosa of individuals with symptomatic BMS, while the margins of the non-neoplastic tongue biopsy served as controls of healthy individuals. Immunohistochemistry was performed to determine the density/mm2 of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells. Similar densities of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells were found in cases of BMS, with a median value of 3.70, 0.70, and 29.24/mm2, respectively, and in the control group, with a median value of 2.60, 0.80, and 26.01/mm2, respectively (p > 0.05). Moreover, the relationship between S100+ and PGP 9.5+ peripheral NF was the same in both groups (p = 0.70). This study demonstrated that there were no alterations in the density and integrity of peripheral NF in the tongue of symptomatic BMS patients. However, the sensitization of peripheral NF in this disease may not depend on mast cell density.

Abstract: There is a lack of evidence on the correlation between salivary biomarkers and subjective measures of dental fear and anxiety in children. This systematic review aimed to retrieve the scientific evidence comparing the results of dental anxiety measured by salivary biomarkers with patient-reported outcomes in pediatric dental setting. The PECOS was as follows: population: pediatric patients aged ≤ 18 years; exposure: patient-reported outcome measures, such as scales and/or questionnaires; comparator: salivary biomarkers; outcome: anxiety, fear, phobia or stress during dental treatment; study design: observational studies or controlled trials. Electronic searches were conducted in PubMed, Scopus, Web of Science, and Ovid databases. Studies that compared scales/questionnaires and salivary biomarkers for the evaluation of dental anxiety, fear, and stress in children/adolescents during dental treatment were included. Certainty of evidence was assessed with GRADE. Risk of bias of the included studies was assessed with the Cochrane tool or the University of Adelaide tool. From the 314 studies identified, eight were included. Participants’ age ranged from three to 13 years. The most used salivary biomarkers and instruments were cortisol and the Dental Subscale of the Children's Fear Survey Schedule, respectively. Most studies showed a weak correlation between objective and subjective measures. The main issues regarding bias were on allocation concealment, blinding of assessors, follow up, and exposure assessment. Certainty of evidence was low/very low. Evidence of salivary biomarkers and patient-reported outcome measures to investigate anxiety, fear and stress in children during in the dental environment is limited. There was no correlation between subjective and objective measures in almost all included studies.

Abstract The aim of this study was to investigate the epidemiological and clinical characteristics of chronic inflammatory periapical diseases in different regions of Brazil and to compare with data from the literature. A multicenter study was carried out in four Brazilian referral centers in oral diagnosis. Histopathological records were reviewed, and all cases diagnosed microscopically as periapical granuloma, radicular cyst, and periapical abscess were included. Demographic and clinical data were collected. Descriptive statistics and Pearson’s chi-square test were performed. A total of 10,381 cases of chronic inflammatory periapical diseases were found (13.8% of 74,931 archived specimens) over a period of 65 years. Radicular cysts were the most common lesion (59.9%). Women (56.1%) with a mean age of 37.01 years old (range 13 to 100 ± 14.42) and people of white skin color (59.2%) were the most affected individuals by chronic inflammatory periapical diseases. The lesions were generally asymptomatic (28.1%), located in the maxilla (60.1%), and posterior region (49.8%). The radicular cysts were larger when compared to periapical granulomas (p < 0.001). The disagreement between the clinical and histopathological diagnoses was higher when the final diagnosis was a periapical granuloma (p < 0.001). Chronic inflammatory periapical diseases continue to be common lesions affecting mainly adults. This should be a consequence of the burden of untreated caries in permanent teeth. Women are more affected and radicular cyst was the most common lesion.

Abstract: FITOPROT, which contains curcuminoids and Bidens pilosa L. extract, is an innovative mucoadhesive formulation indicated for the topical treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with advanced and visible oral squamous cell carcinoma. The formulation is used as a mouthwash directly on tumor tissue of patients with advanced neoplasms, without triggering cancer cell proliferation or tumor invasiveness. Thus, the aim of this study was to evaluate the biological effects of FITOPROT on an oral squamous cell carcinoma cell line (SCC-4). The viability of SCC-4 cells was assessed after exposure to FITOPROT using MTT reduction assay. The effects of the mucoadhesive formulation on cell cycle progression and cell death parameters were evaluated using flow cytometry. In addition, the inflammatory profile of the tumor cells was evaluated using the cytometric bead array (CBA) assay. FITOPROT promoted a concentration-dependent decrease in cell viability and cell cycle arrest at the G2/M phase (p < 0.05). Mitochondrial membrane potential was also altered after exposure to the formulation (p < 0.05), in parallel with a reduction in VEGF and IL-8 production (p = 0.01 and p = 0.05, respectively). In summary, the results indicate that FITOPROT reduces SCC-4 cell viability, promotes cell cycle arrest, modulates mitochondrial membrane potential, and exhibits antiangiogenic and anti-inflammatory properties, thus indicating its potential for topical use in patients with OM and visible tumors in the mouth.

Abstract Regulatory T (Treg) cells can suppress antitumor immune response, but little is known about possible age-related differences in the number of these cells in the microenvironment of oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to determine the number of FoxP3+ Treg cells in the microenvironment of OTSCC in young (≤ 45 years) and older (≥ 60 years) patients, and to correlate the findings with clinicopathological parameters (sex, tumor size/extent, regional lymph node metastasis, clinical staging, and histopathological grade of malignancy). Forty-eight OTSCCs (24 diagnosed in young patients and 24 diagnosed in older patients) were selected. Lymphocytes exhibiting nuclear immunopositivity for FoxP3 were quantified at the tumor invasive front and the results were analyzed statistically using the non-parametric Mann-Whitney test. FoxP3+ lymphocytes were observed in all cases assessed. The number of FoxP3+ lymphocytes in OTSCC tended to be higher in older patients (p = 0.055). Analysis of OTSCC in males and in early clinical stages revealed a higher number of Treg cells in older patients than in young ones (p < 0.05). In older patients, the number of Treg cells tended to be higher in smaller tumors (p = 0.079). Tumors with intense inflammatory infiltrate exhibited a larger number of Treg cells, both in young (p = 0.099) and older patients (p = 0.005). The results suggest a greater participation of Treg cells in immunoinflammatory responses in the microenvironment of OTSCC in older patients, particularly in males and in early stages.

Resumo Pouco se sabe sobre o impacto de um delineamento cruzado nos desfechos de ensaios clínicos randomizados voltados ao comportamento de crianças durante tratamento odontológico. Este estudo objetivou avaliar o efeito da sequência de administração do sedativo, da droga em si e da idade dos participantes no comportamento de crianças que receberam duas consultas odontológicas consecutivas. Dezoito crianças saudáveis não colaboradoras, 2-5 anos de idade, foram randomizadas em dois grupos: G1 - 1,0 mg/kg midazolam oral (primeira sessão) e placebo oral (segunda sessão); G2 - placebo (primeira) e 1,0 mg/kg midazolam oral (segunda). Um observador treinado avaliou o comportamento infantil. Os dados foram analisados por ANOVA de três fatores (alfa=0,05). Midazolam [média(DP); 71,7%(16,5)] e placebo [48,6%(33,1)] resultaram em mais comportamento não cooperativo quando administrados na primeira sessão comparado com a segunda (p=0,001). Com o uso do placebo, crianças de 2-3 anos de idade exibiram mais comportamento não cooperativo [G1 54,9%(36,2); G2 80,5%(8,3)] que as de 4-5 anos de idade (p=0,04). Além disso, a porcentagem de redução do comportamento não cooperativo foi maior em crianças mais velhas em G1 (76,2%) e em crianças mais novas em G2 (32,9%). Considerando a avaliação do comportamento infantil sob sedação, a primeira sessão odontológica influenciou a segunda visita. Os resultados deste estudo confirmam a especulação de que o delineamento cruzado é inadequado para avaliar o comportamento odontológico relacionado à ansiedade/comportamento infantil; os resultados dos ensaios cruzados de sedação odontológica devem ser tratados com extrema cautela.

Abstract Crossover studies continue to be published in spite of warnings about their inherent risks in relation to behavioral outcomes. This study took the opportunity of access to secondary data analysis in order to demonstrate the impact of a crossover design on the outcomes of randomized clinical trials aimed at the behavior of children during dental treatment. We evaluated the effect of the sequence of sedative administration, the sedative and the participant’s age on the behavior of children undergoing two sequential dental visits. Eighteen uncooperative healthy young children were equally randomly assigned to: (G1) 1.0 mg/kg oral midazolam (first session) and oral placebo (second session); (G2) oral placebo (first) and 1.0 mg/kg oral midazolam (second). One trained observer assessed children’s behavior. Data were analyzed by three-way mixed ANOVA. Both midazolam [mean(SD); 71.7%(16.5)] and placebo [48.6%(33.1)] produced more struggling behavior when they were administered in the first session compared to the second one (p=0.001). For the placebo, children aged 2-3 years exhibited more struggling behavior [G1 54.9%(36.2); G2 80.5%(8.3)] than those aged 4-5 years (p=0.04). Also, the reduction of percentage of struggling behavior was higher in G1 for older children (76.2%) and in G2 for younger children (32.9%). There were significant interactions between drug and sequence of administration, and between drug and age. The results of our study confirm the conventional wisdom that crossover study design is inappropriate to evaluate children’s behavior/anxiety related-dental treatment under sedation and the results of crossover studies of dental sedation should be treated with extreme caution.

Abstract The immunoexpression of p16, p53, and Bax in oral tongue squamous cell carcinoma (OTSCC) in young and elderly patients is assessed based on clinical and morphological parameters. The sample consists of 60 OTSCC cases: 30 in young (age ≤ 45 years) and 30 in elderly (age ≥ 60 years) patients. Clinical (tumor size, regional node metastasis, distant metastasis, and clinical stage) and morphological (histological grade of malignancy) parameters were evaluated. Immunohistochemical quantitative analysis was performed using anti-p16, anti-p53, and anti-Bax antibodies. None of the evaluated proteins exhibited statistically significant differences between young and elderly patients (p>0.05). There was a significant association of p16 immunoexpression with clinical parameters in elderly patients. There were no associations of p53 and Bax with any of the clinico-morphological parameters. Correlations between p16 and Bax and between p53 and Bax immunoexpression were observed in young patients (r = 0.363; p = 0.048) and in elderly patients (r = 0.433; p = 0.017), respectively. In conclusion, the assessed proteins could not be used to determine differences in the biological behavior of OTSCC between young and elderly patients. Therefore, all proteins activated the pro-apoptotic pathway of OTSCC in both groups.

This study evaluated the safety of Lafoensia pacari A. St.-Hil. (Lythraceae) stem bark hydroalcoholic extract (LPE) through acute and subchronic toxicological assessments in mice. In the acute toxicity evaluation, a single 2000 mg/kg oral dose of LPE was administered to mice and clinical observations were conducted for 14 days. For subchronic toxicity, LPE doses (6.25-1000 mg/kg) were administered orally for 28 days and biochemical, hematological, histopathological analyses and renal and liver expression of Ki-67 were carried out. The acute oral toxicity evaluation of LPE showed no toxicity in mice and it was was classified as category 5 (LD50>2000-5000 mg/kg). In a repeated dose 28-day toxicity study, LPE (100-1000 mg/kg) led to an increase in reticulocytes, which suggests a possible proliferative effect on blood cells. In addition, LPE (400-1000 mg/kg) of produced alterations in biochemical parameters, although no microscopic changes were found in the organs analyzed. A normal expression of the Ki-67 cell proliferation indicator was observed in the kidney and liver tissues, which suggests that LPE does not bring about changes in the proliferative activity of these organs. In conclusion, LPE should be used with caution, particularly in larger doses over longer periods and also in combination with other medication.

Abstract Lesions of non-endodontic origin may mimic periapical abscess. Osteosarcoma is a rare malignant lesion. Case report The present report describes a case of chondroblastic osteosarcoma in the periapical region of teeth #29, #30, and #31 of an 18-year-old male. Clinical history showed self-reported discomfort in the right posterior gingiva for over a month. Physical examination showed a small expansion and redness of the right mandibular buccal and lingual cortical plates, but no signs of pain or inflammation were observed. All the teeth responded positively to pulp sensibility. Periapical and panoramic radiographs showed slight periapical radiolucency in the roots of teeth #29 and #30, clear periodontal ligament space widening, and evident loss of lamina dura. Incisional biopsy was performed, and based on microscopic findings the diagnosis of chondroblastic osteosarcoma was confirmed. Conclusions Non-endodontic diseases associated with tooth root apex, such as chondroblastic osteosarcoma, should be included in differential diagnosis of jaw lesions that resemble periapical abscess.

ABSTRACT Tooth bleaching is a technique of choice to obtain a harmonious smile, but bleaching agents may damage the dental pulp. Objective: This study evaluated the inflammatory responses of human dental pulp after the use of two bleaching techniques. Material and Methods: Pulp samples were collected from human third molars extracted for orthodontic reasons and divided into three groups: control - no tooth bleaching (CG) (n=7); at-home bleaching with 15% carbamide peroxide (AH) (n = 10), and in-office bleaching with 38% hydrogen peroxide (IO) (n=12). Pulps were removed and stained with hematoxylin-eosin for microscopic analysis of inflammation intensity, collagen degradation, and pulp tissue organization. Immunohistochemistry was used to detect mast cells (tryptase+), blood vessels (CD31+), and macrophages (CD68+). Chi-square, Kruskal-Wallis, and Mann Whitney tests were used for statistical analysis. The level of significance was set at p<.05. Results: The inflammation intensity and the number of macrophages were significantly greater in IO than in AH and CG (p<0.05). The results of CD31+ (blood vessels per mm2) were similar in CG (61.39±20.03), AH (52.29±27.62), and IO (57.43±8.69) groups (p>0.05). No mast cells were found in the pulp samples analyzed. Conclusion: In-office bleaching with 38% hydrogen peroxide resulted in more intense inflammation, higher macrophages migration, and greater pulp damage then at-home bleaching with 15% carbamide peroxide, however, these bleaching techniques did not induce migration of mast cells and increased the number of blood vessels.

Objective The current study aimed to investigate the β-catenin expression in oral leukoplakia (OL) with different degrees of epithelial dysplasia and normal oral mucosa. Material and Methods Formalin-fixed, paraffin-embedded tissue samples of 39 OL (mild dysplasia n=19, moderate dysplasia n=13, and severe dysplasia n=7), and 10 normal oral mucosa (control group) were submitted to immunohistochemical reactions to anti-β-catenin primary antibody. A qualitative β-catenin analysis was performed based on the percentage of positive cells. The cellular location and the epithelial layer were also considered. The Chi-square test and the Fisher’s exact test were used to verify possible differences in the β-catenin expression among the OL groups. A p-value of <0.05 was considered statistically significant. Results Membranous expression of β-catenin in parabasal and basal layers was gradually lost in the higher degrees of epithelial dysplasia. In normal oral mucosa, β-catenin was detected only in the cytoplasmic membrane. However, a significant increase in cytoplasmic β-catenin could be observed between mild and moderate dysplasia (Fisher Exact test - p<0.001) and between mild and severe dysplasia (p<0.001). Conclusions The β-catenin cytoplasmic expression observed in this study may represent the initial stage of modifications in the E-cadherin-catenin complex, along with morphological cellular changes.

Little is known about whether midazolam sedation can reduce salivary cortisol levels and consequently influence children’s behaviour during dental treatment. The aim of this study was to evaluate the effect of midazolam sedation on salivary cortisol and its correlation with children’s behaviour during restorative dental treatment. Eighteen healthy children, aged two to five years, were randomly assigned to two dental treatment appointments, both with physical restraint: oral midazolam 1 mg/kg (MS) and placebo (PS). An observer assessed the children’s behaviour (videos) using the Ohio State University Behavioral Rating Scale (OSUBRS). The children’s saliva was collected just after waking up, on arrival at the dental school, 25 minutes after local anaesthesia, and 25 minutes after the end of the procedure. Salivary cortisol levels were determined using the enzyme-linked immunoabsorbent assay. The data were analysed by bivariate tests and multivariate analysis of variance (5% level). Salivary cortisol levels were lower in the MS group than in the PS group at the time of anaesthesia (p = 0.004), but did not vary during the appointment within sedation (p = 0.319) or placebo (p = 0.080) groups. Children’s behaviour was negative most of the time and did not differ between MS and PS; however, the behaviour (OSUBRS) did not correlate with salivary cortisol levels. Oral midazolam is able to control salivary cortisol levels during dental treatment of pre-schoolers, which might not lead to better clinical behaviour.

O objetivo do estudo foi monitorar tratamentos de canais radiculares (TCR) convencionais e com auxílio de cirurgia periapical. Este estudo prospectivo constituiu de 80 pacientes portadores de infecções primárias e secundárias persistentes e periodontite apical (PA). O índice periapical utilizando tomografia computadorizada de feixe cônico (CBCTPAI) foi utilizado como auxiliar no diagnóstico, planejamento e para determinar a melhor estratégia terapêutica. Apenas 40 pacientes retornaram para o TCR. Em 20 pacientes (26 dentes) com diagnósticos de infecções primárias e PA foram feitos TCR convencionais e monitoramentos por 10 a 36 meses. Em 20 pacientes (31 dentes) com diagnósticos de infecções secundárias persistentes foram submetidos a procedimentos cirúrgicos e acompanhamentos durante 6 a 30 meses. Os resultados mostraram TCR bem sucedidos em 19 de 26 casos, com curas completas das PA (5 de 26 com reparação parcial) em controles de 10 a 36 meses. Para os casos de tratamentos cirúrgicos foram detectadas eficácias das terapêuticas cirúrgicas em 10 de 31 casos com curas completas (10 de 31 casos com reparação parcial) em controles de 6 a 30 meses. O retorno dos pacientes para controle clínico e radiográfico e a obediência ao período de tempo proposto está muito aquém do ideal. Os níveis de sucesso em ambos os protocolos terapêuticos se mostraram elevados. Fracassos no TCR foram detectados mesmo utilizando protocolo clínico com rigoroso padrão.

The aim of this study was to monitor nonsurgical and surgical root canal treatment (RCT) of teeth with primary and secondary infections and apical periodontitis (AP). This prospective clinical study comprised the treatment of 80 patients with primary and persistent secondary infections and AP. Of this initial sample, forty patients did not return. Periapical index using cone beam computed tomography scans (CBCTPAI) was used to aid diagnosis, planning and to determine the better therapeutic strategy. Twenty patients (26 teeth) diagnosed with primary infection and AP received conventional RCT and were followed up for 10 to 36 months. Twenty patients (31 teeth) diagnosed with persistent secondary infection were submitted to periapical surgical and followed up for 6 to 30 months. The results showed RCT successful in 19/26 cases with complete AP healing (5/26 with partial repair) in 10-36 months of follow up. For the surgically managed cases, effectiveness of surgical therapy was detected in 10/31 cases with complete healing (10/31 cases with partial repair) within 6-30 months follow up. The return of patients for clinical and radiographic follow-up, and obedience to the proposed time period was very short from ideal. The levels of success in both therapeutic protocols were high. RCT failures were detected even with rigorous standard clinical protocols.

Introdução:Quando a altura do osso alveolar residual é insuficiente na região posterior da maxila, a elevação do assoalho do seio maxilar visando a viabilizar a instalação de implantes dentários é um procedimento indicado. O enxerto autógeno (EA) de regiões intra ou extraorais é considerado o padrão ouro para esse procedimento. Novas opções de substitutos ósseos vêm surgindo, como o Straumann(r) BoneCeramic (BC) - 60% constituído de hidroxiapatita e 40% de β tricálcio fosfato, 100% sintético -, sendo o material utilizado no presente trabalho.Objetivo: Avaliar e comparar histologicamente o comportamento deste substituto ósseo com o enxerto ósseo autógeno.Material e método:Dez pacientes saudáveis e parcialmente desdentados na região posterior da maxila foram submetidos à elevação do assoalho do seio maxilar previamente à instalação de implantes dentários osseointegráveis, sendo, destes, cinco com EA e cinco com BC. Após seis meses do tempo de integração do enxerto ósseo, as amostras foram coletadas por uma trefina e coradas em hematoxilina e eosina para microscopia.Resultado:Todos os implantes osseointegráveis apresentaram boa estabilidade primária. A análise histológica demonstrou tecido ósseo neoformado viável em quatro das cinco amostras do BC, além de um íntimo contato do tecido ósseo mineralizado recém-formado com as partículas do BC. Em uma amostra do BC, não foi observada formação de osso viável. O tecido ósseo formado a partir do EA e do BC apresentou uma característica histológica similar.Conclusão:O BC se mostrou um material adequado para a elevação do assoalho do seio maxilar previamente à instalação de implantes dentários osseointegráveis.

Introduction:Sinus lift to permit insertion of implants when alveolar residual bone height is insufficient may be considered an effective procedure. The use of autogenous bone from intraoral or extraoral sources is considered as the gold standard for this procedure. New options of bone substitutes have been emphasizing, such as Straumann(r) BoneCeramic (BC), consisting of 60% of hydroxyapatite and 40% of calcium phosphate, 100% synthetic material that was used in this work.Objective:This investigation was designed to evaluate and compare the behavior of a fully synthetic biphasic calcium phosphate (BCP) 60% hydroxyapatite and 40% of β-tricalcium phosphate (Straumann(r) Bone-Ceramic) to the autogenous bone graft (ABG) in maxillary sinus floor elevation procedure prior to installation dental implants.Material and method:Ten healthy patients who were partially edentulous in the posterior maxilla were included in this study and submitted to a unilateral maxillary sinus floor elevation procedure, with grafting using either ABG (control group; 5 patients) or BCP (test group; 5 patients). After 6 months of healing implant sites were created and biopsies taken for histological analyses.Result:A primary stability was achieved with all dental implants after the biopsies. Histological investigation showed a viable new bone tissue formed in 4 of 5 BCP specimens. Also, showed close contact between new bone and BCP particles, in 4 of 5 specimens. In 1 of 5 BCP specimens no viable bone tissue was found. Both ABG and BCP produced similar amounts of newly formed bone, with similar histologic appearance.Conclusion:The results indicate that BCP is a suitable material for sinus augmentation for the placement of dental implants.

Este estudo teve como objetivo avaliar a expressão das metaloproteinases 2 (MMP-2) e 9 (MMP-9) em próstatas caninas normais e com desordens proliferativas, verificando o papel dessas enzimas na remodelação da matriz extracelular (MEC) e no processo de invasão tecidual. Um total de 355 amostras prostáticas foram obtidas, sendo 36 (10,1%) normais, 46 (13,0%) com hiperplasia prostática benigna (HPB), 128 (36,1%) com atrofia inflamatória proliferativa (PIA), 74 (20,8%) com neoplasia intraepitelial prostática (PIN) e 71 (20,0%) com carcinoma prostático (CP). Houve diferença de imunomarcação citoplasmática para MMP-2 e MMP-9 entre o epitélio acinar e o estroma periacinar, quanto aos diferentes diagnósticos. Observou-se correlação entre a expressão de MMP-2 e MMP-9 em relação ao número de células marcadas no epitélio acinar e estroma periacinar, bem como para a intensidade de marcação das células estromais periacinares em próstatas caninas com PIA. Conclui-se que há variação na expressão de MMP-2 e MMP-9 em próstatas caninas de acordo com a lesão, com menor expressão em próstatas caninas normais e com HPB, e maior naquelas com PIA, PIN e CP. Ainda, o microambiente inflamatório na PIA influencia a atividade de ambas as enzimas.

In this study the expression of metalloproteinases 2 (MMP-2) and 9 (MMP-9) in canine normal prostates and with proliferative disorders was evaluated to verify the role of these enzymes in extracellular matrix remodeling (ECM) and in the tissue invasion process. A total of 355 prostatic samples were obtained, from which 36 (10.1%) were normal prostates, 46 (13.0%) with benign prostatic hyperplasia (BPH), 128 (36.1%) with proliferative inflammatory atrophy (PIA), 74 (20.8%) with prostatic intraepithelial neoplasia (PIN), and 71 (20.0%) with prostatic carcinoma (PC). Difference in cytoplasmic immunohistochemical staining of MMP-2 and MMP-9 between acinar epithelium and periacinar stroma was found regarding the different diagnosis. The correlation between MMP-2 and MMP-9 expression in relation to the number of labeled cells in acinar epithelium and periacinar stroma, as well as to the staining intensity in the periacinar stromal cells was evidenced in canine prostates with PIA. In conclusion, MMP-2 and MMP-9 expression has a variation in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in those with PIA, PIN and PC. Moreover, the inflammatory microenvironment of the PIA has influence in the activity of both enzymes.