RESUMO
BACKGROUND: Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer. METHODS: Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b. RESULTS: Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05). CONCLUSIONS: The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Queilite/enzimologia , DNA (Citosina-5-)-Metiltransferases/biossíntese , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias Labiais/enzimologia , Proteínas Repressoras/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/imunologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Queilite/imunologia , Queilite/patologia , Criança , Pré-Escolar , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Feminino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias Labiais/imunologia , Neoplasias Labiais/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Repressoras/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto Jovem , DNA Metiltransferase 3BRESUMO
Matrix metalloproteinases (MMPs), myofibroblasts (MFs) and epithelial proliferation have key roles in neoplastic progression. In this study immunoexpression of MMP-1, MMP-2 and MMP-9, presence of MFs and the epithelial proliferation index were investigated in actinic cheilitis (AC), lip squamous cell carcinoma (LSCC) and mucocele (MUC). Thirty cases of AC, thirty cases of LSCC and twenty cases of MUC were selected for immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, α-smooth muscle actin (α-SMA) and Ki-67. The MMP-1 expression in the epithelial component was higher in the AC than the MUC and LSCC. In the connective tissue, the expression was higher in the LSCC. MMP-2 showed lower epithelial and stromal immunostaining in the LSCC when compared to the AC and MUC. The epithelial staining for MMP-9 was higher in the AC when compared to the LSCC. However, in the connective tissue, the expression was lower in the AC compared to other lesions. The cell proliferation rate was increased in proportion to the severity of dysplasia in the AC, while in the LSCC it was higher in well-differentiated lesions compared to moderately differentiated. There were no statistically significant differences in number of MFs present in the lesions studied. The results suggest that MMPs could affect the biological behaviour of ACs and LSCCs inasmuch as they could participate in the development and progression from premalignant lesions to malignant lesions.
Assuntos
Carcinoma de Células Escamosas/patologia , Queilite/patologia , Neoplasias Labiais/patologia , Metaloproteinases da Matriz/biossíntese , Miofibroblastos/patologia , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas/metabolismo , Queilite/metabolismo , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Neoplasias Labiais/metabolismo , Metaloproteinase 1 da Matriz/análise , Metaloproteinase 1 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinases da Matriz/análise , Lesões Pré-Cancerosas/metabolismoRESUMO
BACKGROUND: Keratocystic odontogenic tumor (KCOT) is a benign tumor that arises sporadically or associated with nevoid basal cell carcinoma syndrome (NBCCS). Its locally aggressive behavior contrasts with its cystic histological appearance. To better understand the interaction between tumor cells and the stroma, the present study aimed to evaluate and compare the immunohistochemical expression of matrix metalloproteinases (MMP-1, -2, and -9), the cellular proliferation index (Ki-67), and the presence of myofibroblasts (MFs) in KCOTs. METHODS: Eleven cases of isolated KCOT (G1) and 12 cases of KCOT associated with NBCCS (G2) were selected for an immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, Ki-67, and α-smooth muscle actin (α-SMA) in MFs. A group of 6 pericoronal follicles (G3) was included as a normal odontogenic tissue control. RESULTS: Significant differences between the G3 and G1/G2 groups regarding the expression of MMP-1, MMP-9 (in connective tissue), and Ki-67 were observed. In KCOT, there was a positive correlation between the Ki-67 antigen and MMP-1 and between MFs and MMP-1 in the parenchyma. No statistical differences were found between G1 and G2 groups. CONCLUSIONS: MMP-1, MMP-9, and proliferative activity appear to play important roles in KCOT pathogenesis. The increased proliferative activity with KCOT was associated with elevated MMP-1 production in the parenchyma, which influenced the growth of the lesion in association with an increased number of MFs.
Assuntos
Saco Dentário/química , Antígeno Ki-67/análise , Metaloproteinase 1 da Matriz/análise , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Miofibroblastos/patologia , Tumores Odontogênicos/química , Actinas/análise , Síndrome do Nevo Basocelular/metabolismo , Síndrome do Nevo Basocelular/patologia , Proliferação de Células , Tecido Conjuntivo/química , Tecido Conjuntivo/patologia , Saco Dentário/patologia , Epitélio/química , Epitélio/patologia , Humanos , Imuno-Histoquímica , Queratinas/análise , Tumores Odontogênicos/patologia , Células Estromais/química , Células Estromais/patologiaRESUMO
The aim of this study was to investigate the osteoclastogenesis process by means of immunohistochemical markers for receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), and cathepsin K (CTSK) antigens in osteolytic lesions of maxillary bones. The sample consisted of 23 radicular cysts (RC), 25 odontogenic keratocysts (OKC), and 25 ameloblastomas (AM). RANKL was statistically higher in RC (49.6±15.2/53.7±18) and OKC (48.6±15.1/51.4±16.8) when compared with AM (37.2±12.5/36.4±13) in the epithelium and connective tissue. OPG was lower in OKC (34.8±18.5) only in connective tissue when compared with RC (44.5±11.2). The expression of RANKL was statistically higher than OPG in RC (epithelium and connective tissue) and OKC (connective tissue). For IL-6, a statistical difference was observed only in the connective tissue between groups, with higher expression in RC (48.2±15) and lower in OKC (22±11.9). The expression of IL-6 was correlated with the intensity of the inflammatory infiltrate. CTSK was statistically higher in AM (34±19) and OKC (29±13.8) compared with RC (19±10.5). According to the results of the present research the bone resorption in cysts and odontogenic tumors occurs through different mechanisms. The ostoclastogenic process in lesions with aggressive clinical behavior, as AM and OKC, seems to be associated with the expression of CTSK. In contrast, lesions with inflammatory etiology, as RC, the expression of IL-6 seems to have an important role in the bone resorption process. The highest expression of RANKL under the expression of OPG also seems to contribute to the growth mechanism of RC and OKC.