RESUMEN
The aim of the present study was to investigate the profile of tumor-infiltrating lymphocytes (TIL) in osteosarcomas of the jaws (OSJ). A total of 21 OSJ samples were analyzed in a retrospective and cross-sectional multicenter study. Immunohistochemistry was performed to determine the recognition of TIL such as CD4+, CD8+, granzyme B+ (GrB), programmed cell death protein+ (PD-1), and cytotoxic T lymphocyte-associated antigen 4+ (CTLA-4) in intratumoral and peripheral (stromal) regions. Positivity was determined based on the percentage and density of TIL+ per square millimeter [1 = absent (< 25 cells/mm2), 2 = low (25 to 130 cells/mm2), and 3 = high (> 130 cells/mm2)]. The association of TIL density with clinicopathologic data was determined by the Mann-Whitney test (p < 0.05). OSJ were positive for CD8+ cells in 45% (n = 9) of cases, for CD4+ cells in 30% (n = 6) of cases, and for CTLA-4+ in 4.8% (n = 1) of cases, with a score of 2 (low TIL) in all cases. All cases were negative for GrB and PD-1 (score 1). No association was observed between immune infiltrate and clinicopathologic findings. OSJ showed a microenvironment with low TIL, including failure of effectiveness of the antitumor immune response (absence of GrB+ cells), and few cells exhibited immunotherapeutic targets, such as CTLA-4 and PD-1.
Asunto(s)
Neoplasias Maxilomandibulares/inmunología , Linfocitos Infiltrantes de Tumor/patología , Osteosarcoma/inmunología , Antígenos CD/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Estudios Transversales , Femenino , Granzimas/inmunología , Humanos , Neoplasias Maxilomandibulares/diagnóstico , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Osteosarcoma/diagnóstico , Osteosarcoma/patología , Receptor de Muerte Celular Programada 1/inmunología , Estudios RetrospectivosRESUMEN
IgG4-related disease is a systemic, multifocal, immune-mediated disorder that can affect multiple organs and may present as a tumor, with rare cases described in the maxillofacial region. A female patient, 53 years old, presenting tumor-like mass in the right mandibular region. Magnetic resonance imaging suggested well circumscribed nodular lesion adjacent to the branch / body of the mandible, extending posteriorly to the masseter muscle. During the surgical procedure of excision, a lesion was observed adhering to the right masseter muscle, but it was possible to remove it completely. Histopathological and immunehistochemical analysis suggested diagnosis of IgG4-related disease, furthermore, IgG4 serum count was increased. Actually, the patient continues on periodical followups in our service and by other specialties. Can be concluded that precise diagnosis of this pathology depends on many factors, being challenging and the treatment involves multidisciplinary evaluation due to the possibility of involvement of several other organs.
La enfermedad relacionada con IgG4 es una condición sistémica, multifocal, mediada por una alteración de la respuesta inmune que puede afectar diferentes órganos o puede presentarse como un tumor, raramente descrito en el área maxilofacial. Se describe el caso de una paciente de sexo femenino de 53 años de edad, presentando una masa tumoral en el ángulo mandibular derecho. La resonancia magnética sugirió un área nodular bien delimitada adyacente al cuerpo mandibular y extendida posteriormente hasta el musculo masetero. Durante la escisión quirúrgica, la lesión se presentaba adherida al musculo de forma lateral siendo posible el retiro total de la lesión. El estudio histopatológico e inmunohistoquimico determinó el diagnóstico de enfermedad relacionada con IgG4 presentando un conteo de igG4 aumentado. Actualmente, la paciente continua con seguimiento por la especialidad. Se puede concluir que el diagnóstico preciso de esta patología depende de algunos factores; el tratamiento debe ser multidsciplinario debido a la inclusión de diferentes órganos en la enfermedad.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Enfermedades Autoinmunes/patología , Inmunoglobulina G , Neoplasias Maxilomandibulares/patología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/diagnóstico por imagen , Inmunohistoquímica , Imagen por Resonancia Magnética , Neoplasias Maxilomandibulares/inmunología , Neoplasias Maxilomandibulares/diagnóstico por imagenRESUMEN
OBJECTIVE: The aim of this study was to investigate the expression of human leukocyte antigens (HLAs) G and E and programmed death-ligand 1 (PD-L1) in oral osteosarcoma (OO) (n = 13). The relationship between the expression of these molecules and histologic grading and metastasis was also evaluated. STUDY DESIGN: HLA-G, HLA-E, and PD-L1 were identified by immunohistochemistry. Samples of normal bone tissue (n = 6) were used as controls. The sections were evaluated using a semiquantitative scoring system with an immunoreactive score, where a score of 0 was considered absent, ≤2 was low, and >2 was high expression. RESULTS: We identified high expression of HLA-G, HLA-E, and PD-L1 by malignant osteoblastic cells in 69.2% of OO cases, which was statistically higher than that in controls (P < .05). Overexpression of these proteins was identified in 8 of 11 samples of high-grade and 1 of 2 samples of low-grade OO. Additionally, 66.6% of patients with metastases (n = 4) and 71.4% of patients without metastases (n = 5) had high expression of HLA-G, HLA-E, and PD-L1 in tumor samples (P > .05). CONCLUSION: OO had high expression of HLA-G, HLA-E, and PD-L1 irrespective of clinicopathologic parameters, including histologic grading and metastasis.
Asunto(s)
Antígeno B7-H1/inmunología , Antígenos HLA-G/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Neoplasias Maxilomandibulares/inmunología , Osteosarcoma/inmunología , Adulto , Anciano , Biomarcadores de Tumor/inmunología , Estudios Transversales , Femenino , Humanos , Inmunohistoquímica , Neoplasias Maxilomandibulares/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Osteosarcoma/patología , Antígenos HLA-ERESUMEN
OBJECTIVES: The present study evaluated the immunohistochemical expression of BMP-2 and BMP-4 and of their receptors (BMPR-IA and BMPR-II) in solid ameloblastoma (SA), unicystic ameloblastoma (UA) and adenomatoid odontogenic tumor (AOT) in order to obtain a better understanding of their role in the development and biological behavior of these tumors. DESIGN: This study analyzed these proteins in 30 cases of SA, 10 cases of UA, and 30 cases of AOT. Immunoexpression was evaluated in the parenchyma and stroma by attributing the following scores: 0, no stained cells; 1, ≤10%; 2, >10% and ≤25%; 3, >25% and ≤50%; 4, >50% and ≤75%.; 5, >75% stained cells. RESULTS: In SAs, positive correlations were observed between the stromal and parenchymal expression of BMP-2 (p<0.001) and between the stromal expression of BMP-2 and BMP-4 (p=0.020), as well as between the stromal expression of BMPR-II and BMP-4 (p=0.001) and the stromal and parenchymal expression of BMPR-II (p<0.001). In UAs, correlations were detected between the stromal and parenchymal expression of BMP-4 (p=0.035) and between the stromal expression of BMP-4 and BMPR-IA (p=0.022). In AOTs, analysis of immunoexpression in the parenchyma revealed positive correlations between all proteins. CONCLUSION: BMPs and their receptors play an important role in the differentiation and development of ameloblastomas and AOTs, but may not explain the different biological behaviors of these lesions. The positive correlation observed in AOTs might be related to the formation of mineralized material in this tumor.
Asunto(s)
Ameloblastoma/metabolismo , Proteína Morfogenética Ósea 2/biosíntesis , Proteína Morfogenética Ósea 4/biosíntesis , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/biosíntesis , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/biosíntesis , Neoplasias Maxilomandibulares/metabolismo , Ameloblastoma/inmunología , Ameloblastoma/patología , Biomarcadores de Tumor/biosíntesis , Proteína Morfogenética Ósea 2/inmunología , Proteína Morfogenética Ósea 4/inmunología , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/inmunología , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/inmunología , Diferenciación Celular/fisiología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Inmunohistoquímica , Neoplasias Maxilomandibulares/inmunología , Neoplasias Maxilomandibulares/patología , Tejido Parenquimatoso/metabolismo , Tejido Parenquimatoso/patología , Células del Estroma/metabolismo , Células del Estroma/patologíaRESUMEN
BACKGROUND: Ameloblastoma is a locally aggressive odontogenic tumor with high rates of recurrence. To better understand the molecular basis of ameloblastoma, tissue microarray (TMA) may represent a useful tool. However, despite TMA has been considered a high-throughput technique for different human neoplasms, it remains to be validated in the ameloblastoma context. Therefore, the objective of this study was to validate TMA for immunohistochemical study of ameloblastoma, determining its most appropriate design. METHODS: Forty cases of ameloblastoma were manually distributed in two TMA blocks assembled in triplicate containing 1.0- and 2.0-mm cores (20 cases each). Immunohistochemistry for cytokeratins 14 and 19, and Bcl-2 and Ki-67 was performed, and semiquantitative analysis was performed. Results obtained with TMA sections were compared to their corresponding conventional whole-section slides (CWSS). RESULTS: Kappa statistical test demonstrated that both 1.0- and 2.0-mm cores assessed as duplicate or triplicate significantly correlated with CWSS, with higher levels obtained using Ki67 (k = 0.98, 0.97, 0.88, 0.87) and CK19 (k = 0.62, 0.58, 0.85, 0.85). There was no significant difference between 1.0- and 2.0-mm cores, and between duplicate and triplicate values. 1.0-mm TMA showed a higher index of core loss (33.74% vs. 4.99%). CONCLUSION: Using a manual arrayer, it was demonstrated that 1.0-mm TMA arranged in duplicate is a valid method for ameloblastoma immunohistochemical study with satisfactory levels of agreement between TMA cylinders and CWSS.
Asunto(s)
Ameloblastoma/inmunología , Ameloblastoma/patología , Neoplasias Maxilomandibulares/inmunología , Neoplasias Maxilomandibulares/patología , Análisis de Matrices Tisulares/métodos , Adulto , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Keratocystic odontogenic tumors (KOTs) are distinct odontogenic lesions frequently affecting the jawbones. They may be associated with nevoid basal cell carcinoma syndrome (NBCCS), and may exhibit disorders involving the extracellular matrix. The aim of this study was to investigate the immunolocalisation of laminin-1 in 20 cases of KOTs in order to contribute to the characterization of this protein, which is little studied in odontogenic tumors. Our results showed laminin-1 in all 20 KOTs studied; its labelling intensity was weak in three cases (15%), moderate in five (25%) and strong in 12 cases (60%). Laminin-1 immunolocalisation was predominantly continuous in 18 (90%) KOTs, including areas of acanthosis, subepithelial split and epithelial buds. Weak immunolabelling was observed in regions exhibiting an inflammatory process, especially in the case of intense inflammation. These findings suggest that laminin-1 does not participate in biological processes such as cystic epithelium-cystic wall separation or the formation of epithelial islands in KOTs. Furthermore, the discontinuous and weak labelling of this protein in the basement membrane of these tumors is probably a consequence of the inflammatory process in the tumor stroma.