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A Clinical And Proteomic Study Of Mycosis Fungoides

Posted on:2007-03-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LiuFull Text:PDF
GTID:1114360218456043Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Mycosis fungoides(MF) is the most common form of cutaneous T-cell lymphoma(CTCL). Its annual incidence is estimated at 0.4/100,000. MF has an indolent clinical course with slow progression over years or sometimes decades, from patches to more infiltrated plaques and eventually to tumors. On histopathology, MF is characterized by an epidermotropic proliferation of small-to medium-sized T lymphocytes with cerebriform nuclei. The prognosis of patients with MF is dependent on stage, and in particular the type and extent of skin lesions and the presence of extracutaneous involvements. The underlying pathogenesis of MF remains an enigma. Despite enormous efforts only a few tumor disease relevant markers have been established that can be used for early diagnosis or for a better therapeutic in MF. The purposes of this study were to update the oriental data of mycosis fungoides in Chinese patients and identify new biomarker for MF by using proteomic approaches.(1) This is a retrospective study to determine the epidemiology, clinicopathologic feature and treatment regime of 51 patients with mycosis fungoides in PUMC hospital during last 22 years.(2) Using ProteinChip(SELDI) technology for the discovery of protein patterns: to compared the serum samples from 14 cases of MF and 17 cases of normal control; to compared the tissue extracted proteins from 17 cases of MF and 27 cases of normal control.(3) Using 2-DE combined with MALDI-TOF mass spectrum to identify the differential expressed proteins: 16 cases of MF and 20 cases of normal control were analysis by this approach.(1) Most patients came from north China, which included 47 cases of mycosis fungoides, 2 cases of folliculotropic mycosis fungoides, and 2 cases of granulomatous slack skin. There were 29 males and 22 females with a mean age of 44.2 years at diagnosis of the disease. Mycosis fungoides characterized by the evolution of patches, plaques and tumors, with some variants and subtypes. 68.6% patients presented with generalized lesions, and 70.6% patients were itchy. Epidermotropism(68.6%) and Pautrier's microabscesses(52.9%) were common histopathologic features. T-cell receptor gene rean'angement was positive in 81.3% cases, which was independent of the histologyical features. 68.6% cases were previously diagnosed as other diseases. Skin-targeted therapies and biologic therapies were effective to relieve the skin rash at early stage of the disease, and combined chemotherapy was generally applied in case with extracutaneous involvement or widespread tumor.(2) By using ProteinChip(SELDI) technology: 14 differential expressed proteins peaks were revealed from serum samples. 25(deposit group) and 24(non-deposit group) differential expressed proteins peaks were found from different group of tissue samples, depend on different tissue prepare method.(3) Thirty-one differential expressed proteins were identified by 2-DE combined MALDI. 22 of these proteins showed increased expression in MF tissue, and 9 of these proteins showed decreased expression in MF tissue. Of these differentially expressed proteins, three were previously reported to be associated with MF, including PPIA, FKBP52, and immunoglobulin heavy chain variable region.Mycosis fungoides has many clinicopathologic variants and subtypes. It should be carefully differentiated with many benign and malignant diseases. ProteinChip(SELDI) and 2-DE combind with MALDI mass spectrum was improved to be able to identify the differential expression proteins in MF sample. These proteins may by serve as an additional parameter for a better insight into the study of the pathogenesis, diagnosis and prognosis of CTCL.
Keywords/Search Tags:mycosis fungoides, retrospective study, ProteinChip, mass spectrum
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