Paulo Rogério de Faria

This study investigated the immunohistochemical expression of histone post-translational modifications (HPTMs) H3K4me2, H3K4me3, and H3K14ac in OSCC and their relationship with metastasis and prognosis. Paraffin-embedded tissue samples of 90 OSCC patients were retrospectively retrieved and immunostained. The sample was divided into primary nonmetastatic (PNM) and primary metastatic (PM) tumors. Nuclear HPTM expression was digitally measured using the integrated optical density index (IOD), and expression levels were divided into low and high based on the median IOD values. Results: All tumor samples were positive. The median H3K14ac IOD was significantly higher in the PM than in the PNM group. High H3K4me2 expression was frequently observed in small and initial tumors, while high H3K4me3 was observed in recurrent OSCC. The ROC curves indicate that H3K14ac might be explored as a screening test for metastasis, showing a sensitivity of 0.81. High H3K4me3-expressing patients had lower survival probabilities and a 3-fold increased risk of death. Conclusions: Our findings suggest that methylation and acetylation of lysine residues 4 and 14 of histone H3 are potential biomarkers of OSCC prognosis and metastasis.

This study analyzed the frequency and distribution of biopsied oral and maxillofacial lesions in a Brazilian geriatric population. Biopsy records of patients aged ≥60 years diagnosed over the last 45 years were retrospectively reviewed. Data on sex, age, anatomical site, and histopathological diagnosis were collected. Absolute and relative frequencies and their associations with clinicopathological variables were evaluated using the chi-square test and the two-proportions Z test. Among 21,367 lesions diagnosed between 1978 and 2023, 2,794 (13.1%) occurred in patients aged ≥60 years, predominantly in the 60–79 age group (90.6%) and in females (54.6%). The most frequent diagnostic categories were reactive lesions (56.6%), neoplasms (25.1%), and cysts/pseudocysts (8.5%). Fibrous hyperplasia (32.9%) and oral squamous cell carcinoma (15%) were the most common individual diagnoses. Females showed higher proportions of reactive lesions, immunological diseases, and bone lesions, with male-to-female ratios of 1:1.7, 1:2.2, and 1:5.7, respectively. The frequency and profile of oral and maxillofacial lesions in older Brazilians are consistent with previous reports. The high burden of inflammatory and neoplastic lesions reflects the cumulative effects of poor oral health and limited healthcare access. These findings highlight the need for strengthened preventive, diagnostic, and long-term oral healthcare strategies, particularly focusing on the aging population.

Background: Oral squamous cell carcinoma (OSCC) is one of the most frequent head and neck cancers. The 4‐nitroquinoline 1‐oxide (4NQO) mouse model of oral carcinogenesis is a well‐established model to investigate the mechanism behind OSCC development, including epigenetic alterations. Studies have shown that histone acetylation is a key regulator of gene expression and may play a role in such a tumor. This study investigates the acetylation of H3K9, H3K14, and H3K27 and the KAT2A gene expression in a sex‐based approach in a 4NQO/ethanol (EtOH)‐induced OSCC mouse model. Methods: A total of 120 C57Bl/6J mice (60 males and 60 females) were divided into four groups ( n = 15). In the first 10 weeks, they were treated with 5 mg/mL propylene glycol (PPG) or 100 μg/mL 4NQO in drinking water, followed by either sterilized water or 8% EtOH for 15 weeks. After euthanasia, tongues were analyzed histopathologically. Immunohistochemistry and qPCR were also employed to study the histones and gene expression. Results: Female mice showed increased H3K9ac and H3K14ac expression from normal mucosa to dysplasia, followed by decreased expression in OSCC. H3K9ac and H3K14ac expression in males was lower in the 4NQO/EtOH group. H3K27ac was higher in dysplastic lesions compared to OSCC, particularly in females. Comparatively, females had higher H3K9ac and H3K14ac expression in the 4NQO/EtOH group than males. KAT2A expression was lower in females treated with PPG/EtOH and 4NQO/H ₂ O than in males. Conclusion: Our results indicate that H3 acetylation and KAT2A gene expression may play a key role in oral carcinogenesis on a sex‐related basis.

Background: Nitric oxide is an important regulator of the epigenetic landscape of cellular homeostatic and pathological states, in which post‐translational modifications of the epigenome‐modulating enzymes are the most well described mechanism. Considering that alterations of the histone acetylation pattern were associated with oral cancer development and progression, the purpose of this study was to analyze the immunohistochemical expression of H3K9ac and H3K27ac at different stages of oral carcinogenesis induced by 4‐nitroquinoline‐N‐oxide (4NQO) in Nos2^+/+ (wild‐type) and Nos2^−/− (knockout) mice.Methods: C57BL/6J and B6.129P2‐Nos2^tm1Lau/J mice were treated with 4NQO in the drinking water at 50 μg/mL for 16 weeks and observed for 8 weeks. Tongues were submitted to histopathological analysis and immunohistochemistry for H3K9ac and H3K27ac expression. The antigen–antibody reaction was analyzed with quickscore (QS).Results: Both histone acetylation marks were expressed in the normal epithelium. QS values were higher in moderate dysplasia of Nos2^−/− mice (p = 0.025) when compared to Nos2^+/+, and mild dysplasia had lower values for H3K9ac when compared to moderate and severe dysplasia in the Nos2^−/− group (p = 0.015). H3K27ac significantly increased from normal mucosa to mild dysplasia in Nos2^+/+ mice (p = 0.007). Additionally, Nos2^+/+ mice had a higher number of H3K27ac‐positive mild dysplasias when compared to Nos2^−/− (p = 0.023).Conclusion: The pattern of histone acetylation changes in murine oral carcinogenesis, mainly when the epithelial lining of the tongue becomes dysplastic, and such epigenetic modifications might be iNOS‐mediated.

Background: Considering that peripheral blood biomarkers are prognostic predictors for several human tumors, this study aimed to comparatively analyze the association of hematological alterations with the incidence of epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) in male and female mice treated with 4‐nitroquinoline‐N‐oxide (4NQO) and ethanol (EtOH).Methods: 120 C57Bl/6J mice (60 males and 60 females) were allocated to four groups (n = 15). They were treated firstly either with 5 mg/mL propylene glycol (PPG) or 100 μg/mL 4NQO in the drinking water for 10 weeks, followed by sterilized water (H₂O) or 8% EtOH (v/v) for 15 weeks, as follows: PPG/H₂O, PPG/EtOH, 4NQO/H₂O, and 4NQO/EtOH (CEUA‐UFU, #020/21). After killing, tongues were collected for histopathological analysis of ED and OSCC. Blood samples were processed for complete blood count and calculation of neutrophil‐to‐lymphocyte ratio (NLR) and systemic immune‐inflammation index (SII).Results: The incidence of OSCC in females from the 4NQO/EtOH group (60%) was lower when compared to males (93%). Neutrophils, NLR, and SII increased from control animals (PPG/H₂O and PPG/EtOH) to ED and OSCC‐bearing male and female mice (4NQO/H₂O and 4NQO/EtOH), while lymphocytes decreased. Females from the 4NQO/H₂O group with ED also had higher neutrophils, NRL, and SII values than females with normal tongues.Conclusion: The low incidence of 4NQO‐ and ethanol‐induced OSCC in females indicates that the sex bias in OSCC may not be associated with extrinsic risk factors alone. Neutrophil and lymphocyte counts, NRL, and SII were significantly altered during multistep carcinogenesis and thus could be explored as biomarkers for ED and OSCC development.

This study aimed to investigate the sociodemographic and clinicopathological data of oral soft tissue hamartomas and choristomas. A cross‐sectional study was delineated to quantitatively analyze oral soft tissue hamartomas and choristomas cases diagnosed between 1978 and 2025 in a Brazilian Oral Pathology Service. The patient’s file raised data regarding the clinical parameters, demographic data, diagnostic imaging, and histopathological features. A review of case reports published in the literature was also performed, analyzed, and compared to our casuistic. Fifteen cases were retrieved from our archive: 60.00% hamartomas and 40.00% choristomas. Females were more affected than males (53.33% vs. 46.67%). The ages of the affected patients varied from newborns to older people. Clinically, most of the lesions were nodular, had an oral mucosa‐like color, and were painless. The buccal gingiva was the most prevalent region affected by the lesions (53.33%). All cases were treated by surgery. Although uncommon, oral soft tissue hamartomas and choristomas mainly affect people of different ages, from newborns to older people. They should be diagnosed promptly to offer better therapeutic management, avoiding invasive treatments that contradict their benign nature.

Atherosclerosis is an age‐related disease affecting the tunica intima of large and medium‐sized arteries. Its occurrence in extracranial head and neck arteries is rare, with only five cases reported. This study is aimed at reporting the sixth case of atherosclerosis of the angular artery, a branch of the facial artery, in an elderly male patient with a history of hypertension. Morphological characterization using special stains and a literature review are included. Clinically, a painless, nodular lesion measuring 1.2 cm was observed at the right labial commissure. The lesion was excised, and atherosclerosis of the angular artery was diagnosed. After 6 months, there was no recurrence or other arterial issues. Despite its rarity in the oral and maxillofacial region, dental clinicians must be aware of this condition and its clinical manifestations, especially in elderly patients with chronic systemic diseases, to establish an accurate diagnosis.