Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), designated recently as a distinct clinicopathologic entity in the World Health Organization Classification, is a neoplasm composed of cytotoxic T-cells that preferentially involves subcutaneous adipose tissue. Histologically, SPTCL is characterized by extensive karyorrhectic debris and tumor necrosis suggesting that apoptotic mechanisms are involved in its pathogenesis. We assessed the apoptotic index (AI) and proliferation rate (PR) of 13 cases of SPTCL by TUNEL test and Ki-67 immunostaining, respectively. We also immunohistochemically assessed for expression of BCL-2 (anti-apoptosis), BAX (pro-apoptosis), and P53 and correlated the results with apoptosis and proliferation. We detected a high AI (median 8.1%) in 11 cases of SPTCL, and 12 cases had low BCL-2 and high BAX expression. BCL-2 expression inversely correlated with AI (P <.001) and BAX (P <.001). We found a low PR (cutoff > or = 25%) in eight (61%) cases. There was an inverse correlation between AI and PR (r = -.58, P =.04). Ten cases were assessed for P53; immunostaining results were heterogeneous but P53 expression correlated with large cell cytologic features. Our findings demonstrate that SPTCLs have a high AI that may be explained by differential expression of BCL-2 and BAX in the neoplastic cells.
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PMID:Apoptosis and proliferation in subcutaneous panniculitis-like T-cell lymphoma. 1206 76

T-cell non-Hodgkin's lymphomas (NHL) represent approximately 10-15% of all lymphomas diagnosed in Western countries. Significant progress has been made over the last 2 decades in defining non-random chromosomal abnormalities. Cytogenetic and molecular analyses have enhanced diagnostic capabilities as well as improved classification and prognostication for T-cell NHL. Gamma-delta T-cell receptor (TCR) clonality now represents the more common TCR rearrangement in subcutaneous panniculitis-like T-cell lymphoma (SCPTCL), hepatosplenic T-cell lymphoma (HSTCL), extranodal NK/T-cell lymphoma, nasal type and enteropathy-type intestinal T-cell lymphoma (EITCL). Non-random, recurrent chromosome abnormalities such as isochrome 7 with HSTCL, complex karyotypes with peripheral T-cell lymphoma, not otherwise characterized (PTCL-NOC), trisomies 3 and 5 with angioimmunoblastic lymphoma (AIL) and t(2;5) with systemic anaplastic T-cell lymphoma have been recognized. Furthermore, identification of relevant protooncogenes and tumor suppressor genes involved in the pathogenesis of T-cell NHL such as the NPM/ALK fusion protein, p53, cyclin dependent kinase inhibitors (p15, p16, p21) and EBV as well as their interplay with the various regulatory pathways of cell cycle progression and apoptosis represent potential candidates for molecular-based therapy. This review presents a detailed analysis of the molecular and genetic perturbations present in mature T-cell lymphomas including discussion of how tumor-specific alterations impact on clinical outcome. Future studies in T-cell NHL are likely to provide additional disease-specific chromosomal translocations and molecular alterations with important translational implications.
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PMID:Molecular etiology of mature T-cell non-Hodgkin's lymphomas. 1245 15

CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas. We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases. The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells. The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.
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PMID:Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan. 1499 42

T-cell non-Hodgkin's lymphoma (NHL) represents approximately 10% to 15% of all lymphomas in Western countries. Patients with T-cell NHL are often treated similarly to patients with intermediate grade B-cell NHL, although many reports have demonstrated lower overall survival rates in patients with T-cell NHL compared to patients with B-cell NHL. Updated classifications have recognized specific clinical and pathologic T-cell entities, such as peripheral T-cell lymphoma, not otherwise characterized, angioimmunoblastic lymphoma, systemic anaplastic T-cell lymphoma, adult T-cell leukemia/lymphoma, subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, and enteropathy-type intestinal T-cell lymphoma. Furthermore, these distinct T-cell NHL subtypes often warrant individualized diagnostic and therapeutic strategies, such as the associated cytophagic histiocytic panniculitis and hemophagocytic syndrome with subcutaneous panniculitis-like T-cell lymphoma, the chromosomal translocation t(2;5), leading to the nucleophosmin anaplastic lymphoma kinase fusion protein, viral pathogenesis of Epstein-Barr virus, human T-cell lymphotropic virus type-1 associated with extranodal NK/T-cell lymphoma nasal type and adult T-cell leukemia/lymphoma, respectively, and the role of radiation therapy in extranodal NK/T-cell lymphoma nasal type. Other active therapeutic agents in T-cell NHL include purine and pyrimidine antimetabolite agents (eg, nucleoside analogues and gemcitabine, respectively), denileukin diftitox, and antinucleoside or retinoic acid with interferon-alpha combination treatment. The exact role of transplantation in patients with T-cell NHL is unknown, but several case series have documented the feasibility of autologous and allogeneic transplant with reported long-term survival rates similar to transplanted B-cell NHL. Identification of relevant proto-oncogenes and tumor suppressor genes involved in the pathogenesis of T-cell NHL, such as the nucleophosmin anaplastic lymphoma kinase fusion protein, p53 and retinoblastoma gene, cyclin-dependent kinase inhibitors, histone deacetylation inhibitors, and infectious etiologies (eg, Epstein-Barr virus and Helicobacter pylori), in addition to their interplay with the various regulatory pathways of cell-cycle progression and apoptosis, represent potential candidates for molecular-based therapy. Prospective multi-institution clinical trials are critically important to determine the most effective treatment regimens that will continue to improve cure rates in these aggressive, yet treatable and often curable, diseases.
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PMID:Treatment of T-cell non-Hodgkin's lymphoma. 1523 6

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.
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PMID:Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review. 1590 Jan 25