ABSTRACT
In this work, a computational scheme is proposed to identify the main combinations of handcrafted descriptors and deep-learned features capable of classifying histological images stained with hematoxylin and eosin. The handcrafted descriptors were those representatives of multiscale and multidimensional fractal techniques (fractal dimension, lacunarity and percolation) applied to quantify the histological images with the corresponding representations via explainable artificial intelligence (xAI) approaches. The deep-learned features were obtained from different convolutional neural networks (DenseNet-121, EfficientNet-b2, Inception-V3, ResNet-50 and VGG-19). The descriptors were investigated through different associations. The most relevant combinations, defined through a ranking algorithm, were analyzed via a heterogeneous ensemble of classifiers with the support vector machine, naive Bayes, random forest and K-nearest neighbors algorithms. The proposed scheme was applied to histological samples representative of breast cancer, colorectal cancer, oral dysplasia and liver tissue. The best results were accuracy rates of 94.83% to 100%, with the identification of pattern ensembles for classifying multiple histological images. The computational scheme indicated solutions exploring a reduced number of features (a maximum of 25 descriptors) and with better performance values than those observed in the literature. The presented information in this study is useful to complement and improve the development of computer-aided diagnosis focused on histological images.
ABSTRACT
This study aimed to analyze the immunohistochemical expression of H3K9ac and H4K12ac in oral leukoplakia (OL) and its association with cell proliferation marker Ki-67 and clinicopathologic data. Paraffin-embedded, formalin-fixed tissue samples from 50 OLs and 15 fragments of the normal oral mucosa (NOM) were submitted to immunohistochemical assay using the streptavidin-biotin-peroxidase method. Quantitative analysis of the antigen-antibody reaction was performed by obtaining integrated optical density (IOD) and the percentage of positive nuclei (PPN) with ImageJ software. OL samples presented higher PPN ( P =0.02) and lower IOD values ( P =0.007) for H4K12ac in comparison to NOM. The area under the receiver operating characteristic curve for PPN and IOD values of H4K12ac immunostaining were 0.70 ( P =0.02) and 0.73 ( P =0.007), respectively. No differences were found between OL and NOM for H3K9ac. Cell proliferation marker Ki-67 had a positive correlation with PPN ( P <0.0001) and IOD ( P =0.0007) for H3K9ac expression and with IOD values ( P =0.002) for H4K12ac expression. The present findings suggest that alterations in the acetylation pattern of H4K12 occur in the early stages of oral carcinogenesis and that both H3K9ac and H4K12ac might have a role in the regulation of epithelial cell proliferation of OL.
Subject(s)
Ki-67 Antigen/metabolism , Mouth Neoplasms , Cell Proliferation , Humans , Leukoplakia, Oral/pathology , Mouth Mucosa/pathology , Mouth Neoplasms/pathologyABSTRACT
The symptoms of chronic kidney disease (CKD) are often not specific or absent in the early stages of this illness. Therefore, there is a demand for developing low cost, non-invasive and highly accurate platforms for CKD diagnostics. We hypothesized that the level of specifics salivary components changes when CKD is emplace, which could be clinically used to discriminate CKD patients from healthy subjects. The present study aimed to compare salivary components between CKD patients and matched control subjects by using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy. The predictive power of salivary components was evaluated by receiver operating characteristic (ROC) curves. Several components were identified, and 4 of them showed different expression (p<0.05) between CKD and control subjects. Thiocyanate (SCN-, 2052 cm-1) and phospholipids/carbohydrates (924 cm-1) vibrational modes using original and second-derivative spectra by ATR-FTIR could potentially be used as salivary biomarkers to differentiate CKD than control subjects. The combination of original and second-derivative spectra by ATR-FTIR of 924 cm-1 vibrational modes could reach 92.8% sensitivity and 85.7% specificity for CKD detection. Despite, the limitation of our investigation, the acquired data indicates that salivary vibrational modes by ATR-FTIR platform should be further explored as an auxiliary diagnostic tool for CKD.
Subject(s)
Renal Insufficiency, Chronic , Saliva , Ataxia Telangiectasia Mutated Proteins , Humans , Sensitivity and Specificity , Spectroscopy, Fourier Transform InfraredABSTRACT
Abstract The symptoms of chronic kidney disease (CKD) are often not specific or absent in the early stages of this illness. Therefore, there is a demand for developing low cost, non-invasive and highly accurate platforms for CKD diagnostics. We hypothesized that the level of specifics salivary components changes when CKD is emplace, which could be clinically used to discriminate CKD patients from healthy subjects. The present study aimed to compare salivary components between CKD patients and matched control subjects by using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy. The predictive power of salivary components was evaluated by receiver operating characteristic (ROC) curves. Several components were identified, and 4 of them showed different expression (p<0.05) between CKD and control subjects. Thiocyanate (SCN-, 2052 cm-1) and phospholipids/carbohydrates (924 cm-1) vibrational modes using original and second-derivative spectra by ATR-FTIR could potentially be used as salivary biomarkers to differentiate CKD than control subjects. The combination of original and second-derivative spectra by ATR-FTIR of 924 cm-1 vibrational modes could reach 92.8% sensitivity and 85.7% specificity for CKD detection. Despite, the limitation of our investigation, the acquired data indicates that salivary vibrational modes by ATR-FTIR platform should be further explored as an auxiliary diagnostic tool for CKD.
Resumo Os sintomas da doença renal crônica (DRC) são frequentemente inespecíficos ou ausentes nos estágios iniciais desta doença. Desta forma, existe uma demanda para o desenvolvimento de plataformas com baixo custo, não-invasivas e com alta acurácia para o diagnóstico da DRC. Nós hipotetizamos que o nível dos componentes salivares se alteram pela DRC, o que pode ser clinicamente utilizado para discriminar pacientes portadores de DRC de indivíduos controles. O objetivo deste estudo foi comparar componentes salivares entre pacientes portadores de DRC e sujeitos controles utilizando um sistema de reflectância total atenuada com espectroscopia infravermelho com transformada em Fourier (ATR-FTIR). O poder preditivo dos componentes salivares foi avaliado pela curva característica de operação do receptor (ROC). Diversos componentes salivares foram identificados e 4 destes apresentaram diferença na expressão (p<0,05) entre DRC e sujeitos controles. O modos vibracionais do tiocianato (2052 cm-1) e de fosfolipídeos/carbohidratos (924 cm-1) utilizando espectros originais e da segunda-derivada pelo ATR-FTIR podem potencialmente ser utilizados como biomarcadores salivares para discriminar a DRC de sujeitos controles. A combinação dos espectros originais e da segunda-derivada pelo ATR-FTIR do modo vibracional 924 cm-1 pode apresentar sensibilidade de 92.8% e especificidade de 85.7% para a detecção da DRC. Este estudo indicou que modos vibracionais da saliva pela plataforma ATR-FTIR podem ser uma ferramenta auxiliar no diagnóstico da DRC.
Subject(s)
Humans , Saliva , Renal Insufficiency, Chronic , Sensitivity and Specificity , Spectroscopy, Fourier Transform Infrared , Ataxia Telangiectasia Mutated ProteinsABSTRACT
AIMS: Studies on epigenetics in oral squamous cell carcinoma (OSCC) are rare. Histone modifications comprise epigenetic mechanisms that perform a key role in gene transcription and may regulate tumour development. Thus, the aim of this study was to determine whether two post-translational histone modifications, i.e. phosphorylation of serine 10 in histone H3 and acetylation of lysine 12 in histone H4, have prognostic value for OSCC patients. METHODS AND RESULTS: Paraffin-embedded tissue samples of 90 patients diagnosed with OSCC were obtained and subjected to immunohistochemical staining with antibodies against histone H3 with phosphorylation of serine 10 (H3S10ph) and histone H4 with acetylation of lysine 12 (H4K12ac). The associations of H3S10ph and H4K12ac expression levels with clinicopathological factors were determined. Five-year survival analysis and univariate and multivariate analyses were also performed. Both H3S10ph and H4K12ac were expressed in the nuclei of tumour cells. A low median of H3S10ph expression was significantly associated with cervical lymph node metastasis. Tumours with high H4K12ac expression were significantly associated with gender, alcohol consumption, and cervical lymph node metastasis. H4K12ac was also shown to have independent prognostic value in the multivariate analysis. Tumours with high H3S10ph expression, size >40 mm, an advanced stage and the presence of cervical lymph node metastases were associated with a better 5-year survival rate. Tumours with low H4K12ac expression, size >40 mm, an advanced stage and cervical lymph node metastasis were associated with a better 5-year survival rate. CONCLUSIONS: These findings suggest that H3S10ph, and mainly H4K12ac, may play a role in OSCC progression and the occurrence of cervical lymph node metastasis. Also, the expression level of H4K12ac could be an independent prognostic factor for OSCC patients.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Histones/metabolism , Mouth Mucosa/metabolism , Mouth Neoplasms/metabolism , Acetylation , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Female , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Mouth Mucosa/pathology , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Neoplasm Staging , Phosphorylation , Prognosis , Survival Analysis , Survival RateABSTRACT
O ameloblastoma é um tumor odontogênico benigno e raro, de comportamento biológico variado, crescimento lento e agressivo. Clinicamente, pode ser classificado em três grupos: multicístico ou sólido, unicístico, periférico ou extraósseo. A variante unicística plexiforme possui um padrão menos agressivo e responde melhor ao tratamento conservador, o qual consiste na marsupialização e posterior curetagem e enucleação. O presente caso relata um ameloblastoma unicístico que ocorreu no ramo mandibular direito de uma criança de 11 anos, submetida ao tratamento conservador, com resultado satisfatório.
Ameloblastoma is a benign and rare odontogenic tumor of varied biological behavior, slow and aggressive growth. Clinically, it can be divided into three groups: multicystic or solid, unicystic, peripheral or extraosseous. The plexiform unicystic form has a less aggressive pattern and responds better to the conservative treatment. This treatment consists of marsupialization and subsequent curettage and enucleation. The present case reports a unicystic ameloblastoma that occurred on the mandible of an 11 year old child, who was submitted to conservative treatment.
ABSTRACT
AIMS: Ameloblastic carcinoma (AMECA) is an odontogenic malignancy that combines the histological features of ameloblastoma and cytological atypia. Because of its rarity, it poses difficulties in diagnosis. The aim of this study was to investigate the socio-demographic data, histopathology, immunohistochemical features, treatment and outcomes of 17 cases. METHODS AND RESULTS: Descriptive statistical analyses were used to portray the clinicopathological data collected, retrospectively. Log-rank tests were performed to determine new prognostic factors. Lesions were immunostained for Ki67, p16, p53, and cytokeratins (CKs), and compared with solid/multicystic ameloblastomas (n = 15). AMECA was mostly diagnosed at a late stage, affecting the posterior mandible of male patients in their fifth decade of life. Recurrence was diagnosed in nearly 90% of treated patients, and metastasis occurred in four patients. The mean number of Ki67-positive cells was 86.4 ± 66 per field. Tumours were focally positive for CK7, CK8, CK14, and CK18, and diffusely positive for CK19, p53, and p16. AMECA showed increased immunoexpression of CK18, CK19, p16, p53 and Ki67 as compared with benign cases. CONCLUSIONS: Our study has contributed to the improved characterization of the epidemiology, prognostic markers, treatment options and outcomes of AMECA. Current criteria must be reviewed to simplify the diagnostic process for these neoplasms.
Subject(s)
Ameloblastoma/pathology , Carcinoma/pathology , Jaw Neoplasms/pathology , Adult , Aged , Ameloblastoma/mortality , Biomarkers, Tumor/analysis , Brazil , Carcinoma/mortality , Female , Humans , Immunohistochemistry , Jaw Neoplasms/mortality , Kaplan-Meier Estimate , Male , Middle Aged , Young AdultABSTRACT
AIMS: Metallothioneins (MTs) are proteins associated with the carcinogenesis and prognosis of various tumours. Previous studies have shown their potential as biomarkers in oral squamous cell carcinoma (OSCC). Aiming to understand more clearly the function of MTs in OSCC we evaluated, for the first time, the gene expression profile of MTs in this neoplasm. MATERIALS AND RESULTS: Tissue samples from 35 cases of tongue and/or floor of mouth OSCC, paired with their corresponding non-neoplastic oral mucosa (NNOM), were retrieved (2007-09). All tissues were analysed for the following genes using TaqMan(®) reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays: MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT3 and MT4. The expression of MT1B and MT1H was seldom detected in both OSCC and NNOM. A significant loss of MT1A, MT1X, MT3 and MT4 expression and gain of MT1F expression was observed in OSCC, compared to NNOM. Cases with MT1G down-regulation exhibited the worst prognoses. The up-regulation of MT1X was restricted to non-metastatic cases, whereas up-regulation of MT3 was related to cases with lymph node metastasis. CONCLUSIONS: Metallothionein mRNA expression is altered significantly in oral squamous cell carcinomas. The expression of MT1G, MT1X and MT3 may aid in the prognostic discrimination of OSCC cases.
Subject(s)
Carcinoma, Squamous Cell/genetics , Metallothionein/genetics , Mouth Neoplasms/genetics , Aged , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/secondary , Down-Regulation , Female , Humans , Male , Matrix Metalloproteinase 16/genetics , Middle Aged , Mouth Mucosa/enzymology , Mouth Neoplasms/pathology , Prognosis , RNA, Messenger/genetics , RNA, Neoplasm/genetics , Tongue Neoplasms/genetics , Tongue Neoplasms/pathology , Up-RegulationABSTRACT
Radiotherapy (RDT) is commonly used for cancer treatment, but high doses of ionizing radiation can directly affect healthy tissues. Positive biological effects of low-level laser therapy (LLLT) on bone repair have been demonstrated; however, this effect on surgical defects of bone previously compromised by radiotherapy has not been evaluated. The aim of this study was to investigate the influence of LLLT (λ = 830 nm) in femur repair after ionizing radiation. Twenty Wistar rats were divided into four groups: control group (GC, n = 5) creation of bone defects (BDs) only; laser group (GL), with BD and LLLT (n = 5); radiotherapy group (GR), submitted to RDT and BD (n = 5); and radiotherapy and laser group (GRL), submitted to RDT, BD, and LLLT (n = 5). GL and GRL received punctual laser application (DE = 210 J/cm(2), P = 50 mW, t = 120 s, and beam diameter of 0.04 cm(2)) immediately after surgery, with 48-h interval during 7 days. Animals were euthanized at 7 days after surgery, and bone sections were evaluated morphometrically with conventional microscopy. Bone repair was only observed in nonirradiated bone, with significant improvement in GL in comparison to GC. GR and GRL did not present any bone neoformation. The result demonstrated a positive local biostimulative effect of LLLT in normal bone. However, LLLT was not able to revert the bone metabolic damage due to ionizing radiation.
Subject(s)
Bone Diseases/etiology , Bone and Bones/radiation effects , Low-Level Light Therapy/methods , Radiotherapy/adverse effects , Animals , Lasers , Male , Radiation, Ionizing , Rats , Rats, Wistar , Wound HealingABSTRACT
An osteolytic tumour of the mandible with prominent expansive growth on the alveolar ridge and displacement of the involved teeth is described in a 28-year-old man. The lesion was diagnosed as a central odontogenic fibroma, an uncommon benign neoplasm derived from dental apparatus, and was removed by curettage. The patient remains asymptomatic after thirteen years of follow-up, which supports the claimed indolent behavior of this poorly documented disease and the adequacy of a conservative surgical treatment.
Subject(s)
Fibroma/surgery , Gingival Neoplasms/surgery , Odontogenic Tumors/surgery , Adult , Fibroma/pathology , Gingival Neoplasms/pathology , Humans , Male , Odontogenic Tumors/pathology , Treatment OutcomeABSTRACT
BACKGROUND: The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas. METHODS: Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry. RESULTS: Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4+ (> or = 66.7%) or CD8+ T-cells (<33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity > or = 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P < 0.05). The relative percentage of CD4+ T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (P < 0.05) while the proportion of CD8+ T-cells was higher in MC-BMT without metastasis. Consequently, the CD4+/CD8+ ratio was significantly increased in both groups with metastasis. Regardless of the tumor type, the animals with high proportions of CD4+ and low CD8+ T-cells had decreased survival rates. CONCLUSION: The intensity of lymphocytic infiltrate and probably the relative abundance of the CD4+ and CD8+ T-lymphocytes may represent important survival prognostic biomarkers for canine mammary carcinomas.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Carcinoma/veterinary , Dog Diseases/immunology , Immunophenotyping/veterinary , Inflammation/veterinary , Lymphocytes, Tumor-Infiltrating/immunology , Mammary Neoplasms, Animal/immunology , Animals , CD4-CD8 Ratio , Carcinoma/immunology , Carcinoma/secondary , Carcinoma/therapy , Dog Diseases/pathology , Dog Diseases/therapy , Dogs , Female , Flow Cytometry , Inflammation/immunology , Inflammation/pathology , Inflammation/therapy , Mammary Neoplasms, Animal/pathology , Mammary Neoplasms, Animal/therapy , Neoplasm Staging , Prognosis , Time FactorsABSTRACT
BACKGROUND: Information on the biology of metastasis development in salivary gland tumors is scarce. Since angiogenesis seems associated with this phenomenon in other tumors, we sought to compare salivary gland tumors with diverse metastatic behavior in order to improve the knowledge and management of these lesions. METHODS: Samples from the most important salivary gland tumors were segregated according to its metastatic behavior and submitted to routine immunohistochemistry to identify vessels positive for CD105 expression. Frequency of positive cases and intratumoral microvessel density (IMD) was compared among the group of lesions. RESULTS: CD105 positive vessels were absent in normal salivary gland tissue, were rare in pleomorphic adenomas and adenoid cystic carcinomas (ACC), more common in polymorphous low-grade adenocarcinomas and highest in mucoepidermoid carcinomas. Only ACC with such feature were metastatic. IMD was higher in malignant rather than benign tumors. CONCLUSION: Immunostaining of CD105 in salivary gland tumors implies participation of angiogenesis in the development of malignant lesions, as well as some role for myoepithelial cells in the control of new vessel formation. In addition, suggest that ACC with positive CD105 vessels are at higher risk for metastasis.
Subject(s)
Antigens, CD/metabolism , Epithelium/metabolism , Neovascularization, Pathologic/metabolism , Receptors, Cell Surface/metabolism , Salivary Gland Neoplasms/blood supply , Salivary Gland Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD/genetics , Child , Endoglin , Epithelium/blood supply , Epithelium/pathology , Female , Gene Expression , Humans , Male , Middle Aged , Neoplasm Metastasis , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Receptors, Cell Surface/genetics , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Salivary Glands/blood supply , Salivary Glands/cytology , Salivary Glands/metabolism , Salivary Glands/pathology , Young AdultABSTRACT
Keratoacanthoma (KA) is a self-limited benign epithelial proliferative lesion that eventually presents with very similar clinical features to squamous cell carcinoma. Many KA appear in the vermilion border of the lips and therefore dental professionals must be familiar of the disease. This article reports the case of a 40-year-old female patient presenting with an exophytic ulcerative tumor in her lower lip that resolved after incisional biopsy. Photographic documentation of the case is presented and topics that are relevant to the clinical management of the disease are addressed.
Subject(s)
Adult , Female , Humans , Keratoacanthoma/pathology , Lip Diseases/pathology , Carcinoma, Squamous Cell/diagnosis , Diagnosis, Differential , Lip Neoplasms/diagnosis , Remission, SpontaneousABSTRACT
Keratoacanthoma (KA) is a self-limited benign epithelial proliferative lesion that eventually presents with very similar clinical features to squamous cell carcinoma. Many KA appear in the vermilion border of the lips and therefore dental professionals must be familiar of the disease. This article reports the case of a 40-year-old female patient presenting with an exophytic ulcerative tumor in her lower lip that resolved after incisional biopsy. Photographic documentation of the case is presented and topics that are relevant to the clinical management of the disease are addressed.
Subject(s)
Keratoacanthoma/pathology , Lip Diseases/pathology , Adult , Carcinoma, Squamous Cell/diagnosis , Diagnosis, Differential , Female , Humans , Lip Neoplasms/diagnosis , Remission, SpontaneousABSTRACT
BACKGROUND: In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. METHODS: Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, beta-catenin, and E-cadherin. RESULTS: After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. CONCLUSION: There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.
Subject(s)
Mammary Neoplasms, Animal/pathology , Salivary Gland Neoplasms/pathology , Adenoma, Pleomorphic/metabolism , Adenoma, Pleomorphic/pathology , Adult , Animals , Dogs , Female , Humans , Male , Mammary Neoplasms, Animal/metabolism , Middle Aged , Salivary Gland Neoplasms/metabolism , Species SpecificityABSTRACT
Beta-catenin plays a central role in cadherin/catenin cell-cell adhesion complex and is involved in cell signaling pathway. Change in beta-catenin distribution has been associated with several human cancers including salivary gland tumors. We studied the immunolocalization of beta-catenin in a series of pleomorphic adenomas (PA) and carcinomas ex-pleomorphic adenomas (Ca ex-PA). Ten samples of PA and ten of Ca ex-PA were evaluated by immunohistochemistry using streptavidin-biotin-peroxidase technique and a monoclonal antibody against beta-catenin (E-5). Cell membrane/cytoplasmic staining of beta-catenin was observed in normal gland parenchyma, PA, and in well-differentiated Ca ex-PA. Cytoplasmic/nuclear beta-catenin staining was observed in poorly differentiated carcinomas and, interestingly, in one case of PA. Our data showed decreased cell membrane beta-catenin expression in higher-grade tumors suggesting that beta-catenin may play an important role in histologic differentiation and transition to malignant phenotype of Ca ex-PA.
Subject(s)
Adenoma, Pleomorphic/chemistry , Carcinoma/chemistry , Salivary Gland Neoplasms/chemistry , beta Catenin/analysis , Adenoma, Pleomorphic/pathology , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Cell Membrane/chemistry , Child, Preschool , Cytoplasm/chemistry , Female , Humans , Immunohistochemistry , Male , Middle Aged , Salivary Gland Neoplasms/pathologyABSTRACT
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent skin cancer. Its pathogeny is linked to genotoxic effects of actinic radiation exposure, especially to ultraviolet wavelength. Metallothionein (MT) is a low-molecular weight protein with high affinity for heavy metal. Its intracellular function has been related to heavy metals and free-radical detoxification, although many studies linked MT to protective action against actinic mutagenesis. In other way, overexpression in malignant tumors has been related to worse prognosis. We aimed to evaluate MT immunohistochemical expression in skin cancer associated to actinic radiation. Twenty-six BCC cases, 20 SCC, and 6 normal skin fragments were investigated. Immunohistochemical assay were performed by streptavidin-biotin-peroxidase technique with standard monoclonal antibody (E9). In normal skin, immunostaining was observed in basal layer of the epithelium. In the epithelium adjacent to tumors, suprabasal layer was also intensely labeled. Mean MT immunostaining indices were 18.5+21.2% for BCC and 69.1+14.4% for SCC. This difference was statistically significant. Higher MT expression in SCC as compared with BCC suggests association with tumoral aggressiveness.
Subject(s)
Carcinoma, Basal Cell/metabolism , Carcinoma, Squamous Cell/metabolism , Metallothionein/metabolism , Skin Neoplasms/metabolism , Ultraviolet Rays , Aged , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/pathology , Female , Humans , Immunohistochemistry , Male , Skin Neoplasms/pathologyABSTRACT
RESUMEN: Las alteraciones de la p53 han sido implicadas en el proceso de carcinogénesis oral. El carcinoma de células escamosas es la malignidad más común de la cavidad oral, siendo la lengua el sitio afectado con mayor frecuencia. El objetivo de este estudio ha sido comparar la inmunoexpresión de la p53 en 43 muestras de carcinoma de células escamosas de la cavidad oral (CCEOs) de 5 sitios anatómicos distintos: lengua, piso bucal, encía/crista alveolar, región retromolar y otras regiones de la cavidad oral. Treinta y tres lesiones (el 76,8%) han mostrado positividad para la p53 (índice promedio del 48,37%). No han sido encontradas diferencias estadísticamente significantes entre la expresión de p53 y los diferentes sitios orales analizados. Similarmente, no han sido encontradas diferencias cuando comparadas las lesiones de lengua con los sitios remanentes. Estos resultados parecen sugerir la no existencia de diferencias entre los sitios anatómicos orales en cuanto a la inmunoexpresión de la p53. Además de eso, otros mecanismos, además de las alteraciones de la p53, en los CCEs de lengua, pueden tener relevancia en la mayor agresividad tumoral encontrada en este sitio anatómico en particular.
Subject(s)
Male , Humans , Female , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/chemistry , Mouth Neoplasms/chemically induced , Mouth Neoplasms/immunology , Mouth Neoplasms/chemistry , Immunohistochemistry/methods , Immunohistochemistry , /analysis , /adverse effects , /chemical synthesisABSTRACT
Despite studies concerning toxic reactions related to amalgam components in the literature, few studies have been devoted to evaluate local noxious effects of amalgam tattoos (AT) on biological tissues. In addition, little is known about activation of inflammatory cells by mucosa-implanted amalgam debris. Tissue reaction to AT depends on the particle size. Human leukocyte antigen DR (HLA-DR) is an activation marker of inflammatory cells associated with antigen presentation. Metallothioneins (MT) are proteins involved with metal detoxication, including mercury and silver. The purpose of the present study was to investigate the immunolocalization of HLA-DR and MT in AT with large or powdered particles. Paraffin-embedded AT tissue blocks were sectioned and subjected to immunohistochemistry for HLA-DR and MT localization. The results demonstrated a dense mononuclear inflammatory infiltrate associated with large and powdered debris and positivity for HLA-DR and MT in inflammatory cells. While blood vessel walls and connective fibers impregnated with powdered particles were negative for HLA-DR, they were positive for MT. In addition, wherever epithelial basement membrane impregnation by powdered amalgam particles was observed, a strong positivity for MT was detected. These findings demonstrate that residual elements of AT still have noxious local effects over tissues.
Subject(s)
Dental Amalgam/adverse effects , HLA-DR Antigens/analysis , Metallothionein/analysis , Pigmentation Disorders/immunology , Pigmentation Disorders/metabolism , Argyria/etiology , Argyria/immunology , Argyria/metabolism , Foreign-Body Reaction , Humans , Immunoenzyme Techniques , Leukocytes, Mononuclear , Mouth Mucosa/chemistry , Particle Size , Pigmentation Disorders/chemically inducedABSTRACT
Poucos estudos têm investigado a toxicidade tecidual local das tatuagens por amálgama (TA), embora diversos trabalhos demonstrem efeitos nocivos desse material restaurador. Pouco se sabe sobre a ativação de células inflamatórias nesse tipo de lesão. A reação tecidual contra os restos de amálgama varia com o tamanho das partículas implantadas. O antígeno leucocitário humano DR (HLA-DR) está associado com a ativação de células inflamatórias, sendo relacionado à apresentação de antígeno. Metalotioneínas (MT) são proteínas envolvidas com neutralização de metais pesados, tais como mercúrio e prata. O objetivo do presente trabalho foi investigar a imunolocalização de HLA-DR e MT em TA compostas por depósitos teciduais de diferentes tamanhos. Cortes histológicos de lesões fixadas em formol e embebidas em parafina foram submetidos a técnica imunoistoquímica para a detecção dos antígenos mencionados. Os resultados demonstraram denso infiltrado inflamatório associado com partículas grandes ou pulverizadas, observando-se presença de células HLA-DR e MT positivas. Paredes de vasos sangüíneos e fibras de tecido conjuntivo impregnadas por restos de amálgama foram negativas para HLA-DR, mas positivas para MT. Impregnação da membrana basal por partículas de amálgama correspondia a forte positividade para MT no epitélio. Esses resultados demonstram a existência de efeitos nocivos locais das TA sobre os tecidos.