P63 is a recently discovered gene harbouring different isoforms by alternate splicing. The two main isoforms, TAp63 and Delta Np63, have opposite functions, being responsible for cell-cycle arrest and cell proliferation, respectively. In addition, new isoforms have been described with the same sequence as TAp63 and Delta Np63, but lacking exon 4 (Delta 4Tap63 and Delta Np73L). P63 as detected using immunohistochemistry is present in squamous cell carcinomas. To better define the role of p63 in squamous cell carcinomas of the oral cavity (OSCC), 39 patients were investigated using immunohistochemical analysis with a monoclonal antibody recognising all p63 isoforms and an anti-Ki67 antibody. Reverse-transcription polymerase chain reaction (PCR) and nested PCR were also performed using isoform-specific primers to evaluate the p63 mRNA expression pattern. Using immunohistochemistry, p63 was always present in OSCC, and its distribution was similar to that of Ki67. The percentage of positive cells increased from normal to neoplastic mucosa, but there was no relationship between the number of p63 positive cells and prognosis. P63 mRNA was found in all patients. The truncated isoforms Delta 4TAp63 and Delta Np73L were more frequently expressed in patients presenting with metastases. Delta Np73L was found in 66.6% of tumours with lymph-node metastases, but in only 33.3% of those devoid of lymph-node metastases at presentation. An impaired expression of the p63 isoforms might favour cell proliferation and indirectly enhance the metastasising capacity of OSCC.

Isolated central nervous system (CNS) relapse was evaluated in terms of incidence, risk factors, and outcome in a consecutive cohort of 175 patients with aggressive non-Hodgkin's lymphoma in which no case of lymphoblastic or Burkitt's lymphoma was encountered. All these patients had obtained a complete remission with first-line treatment and none had received prophylactic CNS treatment at diagnosis. Nine patients (5.2%) developed isolated CNS relapse after a median of 8 months from diagnosis. CNS involvement was documented by cerebrospinal fluid (CSF) cytology in 4 patients and on the basis of radiologic and clinical features in 5 others. Factors significantly associated with a greater likelihood of CNS relapse were advanced stage, B symptoms, bone marrow involvement, and high LDH levels in univariate analysis with only advanced stage being of significance in multivariate analysis. All relapsed CNS lymphoma patients died within a median time of 4 months from the disease recurrence, confirming the poor prognosis after CNS relapse and stressing the need to develop new treatment strategies for patients at high risk of CNS recurrence.

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Lymphoblastic lymphoma (LBL) in adult patients is recognized as a particular entity in the high-grade non-Hodgkin's lymphoma (HG-NHL) group with characteristic clinical and prognostic features. Initially, polychemotherapy normally used in HG-NHL failed to produce long-term relapse-free survival because of progression disease in the CNS and in the bone marrow. Subsequently, the intensification of therapy using multimodality aggressive acute lymphoblastic leukemia (ALL) treatments led to an increase in long-term relapse-free survival. We analyzed retrospectively 53 adult patients with LBL according to the Kiel classification and the criteria by Nathwani et al. Therapeutic modifications depended upon the different times of diagnosis. Twenty-one patients received the modified L17 regimen, 13 patients were treated with the L0288 regimen, and 19 patients were submitted to the L20 protocol. There was no significant differences in CR rates among the three protocols: 48% vs 54% vs 63%, respectively. Nineteen of 29 patients who achieved CR were alive and relapse-free at a median follow-up of 84 months. Ten of the CR patients underwent autologous bone marrow transplantation (ABMT) to consolidate the first response and 7 of them are alive and relapse-free. Early stage of disease, age < 30 years, low LDH levels, the absence of leukemic phase at diagnosis, and, in particular the attainment of CR were all features of patients with good prognosis. Our study confirms the role of intensive polychemotherapeutic regimens including CNS prophylaxis, the significance of a score model of prognostic factors, and of the role of ABMT (or allogeneic bone marrow transplantation) in the treatment of adult LBL.