RESUMO
OBJECTIVE: The aim of this study was to analyze the immunohistochemical expression of Skp2 protein in 38 oral nevi and 11 primary oral melanomas. STUDY DESIGN: Expression of this ubiquitin protein was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index (LI) was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting 1000 cells per slide. RESULTS: Skp2 protein was rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showed high levels of this protein. CONCLUSION: These results indicate that Skp2 protein may play a role in the development and progression of oral melanomas, and it also could be useful as an immunohistochemical marker for differential diagnosis of oral benign and malignant melanocytic lesions.
Assuntos
Melanoma/metabolismo , Neoplasias Bucais/metabolismo , Nevo/metabolismo , Proteínas Quinases Associadas a Fase S/biossíntese , Adolescente , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/química , Pessoa de Meia-Idade , Neoplasias Bucais/química , Nevo/química , Proteínas Quinases Associadas a Fase S/análise , Adulto JovemRESUMO
The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions.
Assuntos
Biomarcadores Tumorais/análise , Melanoma/metabolismo , Neoplasias Bucais/metabolismo , Nevo/metabolismo , Adolescente , Adulto , Idoso , Ciclina D1/análise , Ciclina D1/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p21/análise , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p27/análise , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Nevo/diagnóstico , Adulto JovemRESUMO
The MHC class I chain-related protein A (MICA) is an inducible molecule almost not expressed by normal cells but strongly up-regulated in tumor cells. MICA-expressing cells are recognized by natural killer (NK) cells, CD8+ abTCR and gdTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA triggers IFN-g secretion and cytotoxicity against malignant cells. Although most solid tumors express MICA and this molecule is a target during immune surveillance against tumors, it has been observed that high grade tumors from different histotypes express low amounts of cell surface MICA due to a metalloprotease-induced shedding. Also, melanomas develop after a complex process of neotransformation of normal melanocytes. However, the expression of MICA in premalignant stages (primary human quiescent melanocytic nevi) remains unknown. Here, we assessed expression of MICA by flow cytometry using cell suspensions from 15 primary nevi isolated from 11 patients. When collected material was abundant, cell lysates were prepared and MICA expression was also analyzed by Western blot. We observed that MICA was undetectable in the 15 primary nevi (intradermic, junction, mixed, lentigo and congenital samples) as well as in normal skin, benign lesions (seborrheic keratosis), premalignant lesions (actinic keratosis) and benign basocellular cancer. Conversely, a primary recently diagnosed melanoma showed intense cell surface MICA. We conclude that the onset of MICA expression is a tightly regulated process that occurs after melanocytes trespass the stage of malignant transformation. Thus, analysis of MICA expression in tissue sections of skin samples may constitute a useful marker to differentiate between benign and malignant nevi.
Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Nevo/metabolismo , Lesões Pré-Cancerosas/metabolismo , Neoplasias Cutâneas/metabolismo , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Nevo/imunologia , Nevo/patologia , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologiaRESUMO
Cutaneous melanoma is an aggressive cancer derived from skin melanocytes. Tissue microarrays are being used to evaluate the roles of numerous proteins implicated in some of the pathways involved in melanoma pathogenesis. Based on a previous study using a complementary DNA microarray platform, the aim of this study was to evaluate the immunohistochemical expression of the adhesion and communication molecules connexin 43, desmocollin 3, cytokeratin 5, kallikrein 6, and kallikrein 7 in a melanoma progression model. We analyzed 59 common nevi, 22 atypical nevi, and 162 invasive and 29 metastatic melanomas on tissue microarrays using digital microscopy. The expression of desmocollin 3 and connexin 43 was higher in melanomas (P < .001). Kallikrein 6 expression was higher in melanomas than in common nevi (P < .006). The expression of cytokeratin 5 and kallikrein 7 was higher in atypical nevi than in melanomas (P < .001) and was higher in melanomas than in common nevi (P < .001). The expression of desmocollin 3 and connexin 43 in melanomas indicates loss of cell-cell interactions, which starts in the early steps of the melanoma progression model. Keratin expression in melanomas may play a particular role during melanocyte development. The expression of kallikrein 7 and kallikrein 6 in melanomas may be responsible for the loss of cell-cell adhesion.