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.
In this paper, we propose an approach based on ensemble learning to classify histology tissues stained with hematoxylin and eosin. The proposal was applied to representative images of colorectal ...cancer, oral epithelial dysplasia, non-Hodgkin’s lymphoma, and liver tissues (the classification of gender and age from liver tissue samples). The ensemble learning considered multiple combinations of techniques that are commonly used to develop computer-aided diagnosis methods in medical imaging. The feature extraction was defined with different descriptors, exploring the deep learning and handcrafted methods. The deep-learned features were obtained using five different convolutional neural network architectures. The handcrafted features were representatives of fractal techniques (multidimensional and multiscale approaches), Haralick descriptors, and local binary patterns. A two-stage feature selection process (ranking with metaheuristics) was defined to obtain the main combinations of descriptors and, consequently, techniques. Each combination was tested through a rigorous ensemble process, exploring heterogeneous classifiers, such as Random Forest, Support Vector Machine, K-Nearest Neighbors, Logistic Regression, and Naive Bayes. The ensemble learning presented here provided accuracy rates from 90.72% to 100.00% and offered relevant information about the combinations of techniques in multiple histological images and the main features present in the top-performing solutions, using smaller sets of descriptors (limited to a maximum of 53), which involved each ensemble process and solutions that have not yet been explored. The developed methodology, i.e., making the knowledge of each ensemble learning comprehensible to specialists, complements the main contributions of this study to supporting the development of computer-aided diagnosis systems for histological images.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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