Análise comparativa da expressão e atividade das metaloproteinases 2 e 9 e de seus inibidores teciduais nas lesões cutâneas das variantes poiquilodérmica e clássica da micose fungoide [thesis]

Roberta Vasconcelos Berg
Análise comparativa da expressão e atividade das metaloproteinases 2 e 9 e de seus inibidores teciduais nas lesões cutâneas das variantes poiquilodérmica e clássica da micose fungoide. AGRADECIMENTOS Ao Prof. Dr. José Antonio Sanches, meu orientador e amigo querido, agradeço pela confiança, amizade, apoio e por me inspirar dia a dia a exercer a minha profissão. À minha mãe, Nanci Vasconcelos, por me impulsionar a ser quem eu sou e por me incentivar a iniciar este trabalho. Ao meu pai,
more » ... meu pai, Gualberto, que de algum lugar me protege e me inspira a seguir o caminho do saber. Ao meu irmão, Gabriel, por estar sempre ao meu lado. Ao meu marido Felipe Berg, pelo suporte, parceria e amor ao longo destes anos. A todos aqueles que me ajudaram neste trabalho e fizeram seu acréscimo para que essa tese fosse possível: Documentação; 2011. Abreviatura dos títulos dos periódicos de acordo com List of Journals in Index Medicus. Vasconcelos R. Análise comparativa da expressão e atividade das metaloproteinases 2 e 9 e de seus inibidores teciduais nas lesões cutâneas das variantes poiqulodérmica e clássica da micose fungoide [tese]. São ABSTRACT Berg RV. A comparative analysis of the expression and activity of metalloproteinases 2 and 9 and their tissue inhibitors in cutaneous lesions of poikilodermatous and classic variants of mycosis fungoides [Thesis]. São Introduction: poikilodermatous mycosis fungoides (pMF) is a clinical variant of mycosis fungoides (MF). It is more indolent than classic MF and is characterized by the presence of poikiloderma. The matrix metalloproteinases (MMPs) and their specific inhibitors TIMP (Tissue Inhibitors of Metalloproteinases) are involved in oncogenesis. Specifically, MMP2 and MMP9 and their inhibitors, TIMP-2 and TIMP-1, respectively, have been related to prognosis in tumors. There are few studies on MMP and none on the role of TIMPs in MF. Objectives: To evaluate if there is a relationship between the presence and activity of MMP2 and MMP9 and their inhibitors TIMP2 and TIMP1, and the aggressiveness of MF. To describe a casuistic of poikilodermatous mycosis fungoides in an outpatient clinic in the Dermatological Division of Hospital das Clinicas of University of Sao Paulo Medical School. Methods: Retrospective analysis of 54 cases of pMF, this included 25 localized pMF (LpMF), 14 generalized pMF (GpMF) and 15 mixed pMF. For the analysis of MMPs and TIMPs, the pMF groups were compared with 7 normal skin samples (NS), 10 cases of initial classical MF (cMF), 9 cases of non-transformed tumor MF (nt MFT) and 10 transformed tumor MF (t MFT). Results: The proportion of women : men was 2.44. The pMFs groups showed a longer period of time from the first symptoms to the diagnosis than the cMF group. The GpMF group had a higher incidence of pityriasis lichenoides chronica-like lesions (PLC) (79%) than the other groups. There was a high incidence of hypopigmented MF (62%) in the mixed pMF group. Histology showed typical characteristics of MF and, additionally, atrophy, telangiectasia and pigmentary alterations compatible with pMF. At immunohistochemistry the cases were predominantly CD3+, CD4+, CD7-, CD8-phenotype in all groups, and the pMF groups had a significantly lower prevalence of CD8+ phenotype than the cMF group. The GPMF group showed low positivity for clonality of the T-cell receptor at the T skin (12.5%) compared to the other groups. The MMP2 was more present in the epidermis for the cMF and pMF groups compared to MFT. In the superficial dermis, the cMF, LpMF and GpMF groups showed more MMP2 than normal skin, however there was no statistical difference between the three groups. There was no statistical difference in the presence of MMP2 in the deep dermis between the groups. The zymography showed higher MMP2 activity in the MFT group. There was no TIMP-2 expression by the normal epidermis. The epidermis of cMF and pMFs groups marked TIMP-2 in a similar way, but at a lower intensity than the MFT groups. In the superficial dermis, there was no statistical difference between the cMF and pMFs groups. TIMP-2 was more expressed in the deep dermis of the two MFT groups compared to all of the other groups. In the epidermis and superficial dermis, the MMP9 was more
doi:10.11606/t.5.2016.tde-22082016-111332 fatcat:pws7cebbrfgg3ej6j7idddfz44