Bone marrow histopathological and molecular changes of small B-cell lymphomas after rituximab therapy: comparison with clinical response and patients outcome.

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.

Beta-catenin gene analysis in oral squamous cell carcinoma.

The molecular mechanisms involved in the development of oral squamous cell carcinomas (OSCC) are not yet well understood. Evidence of recent studies suggests that aberrant beta-catenin signalling may participate in the neoplastic transformation and that it is implicated in the development of several tumours. Beta-catenin is a component of the catenin family and plays a crucial role in cadherin mediated cell adhesion. However, it has recently been shown that beta-catenin is also involved in other functions such as intracellular signalling and the regulation of gene transcription. The aim of this study is to evaluate the presence of mutation in exon 3 of the beta-catenin gene in 20 OSCC cell lines. DNA was extracted using Qiagen Qiamp DNA minikit and a region encompassing the exon 3 of beta-catenin gene was amplified using a single PCR assay. The PCR products were analysed by SSCP and direct sequencing to detect any mutation of the gene. Most of the cell lines examined showed, by immunofluorescence, a beta-catenin delocalization. SSCP and sequence analysis of the PCR products did not show any mutation of the beta-catenin gene in any of the cell lines. In conclusion, although aberrant expressions or abnormal localization of beta-catenin have been detected in several OSCC cells, it appears that this finding has no relationship with beta-catenin gene mutations.