NO EVIDENCE OF GENOMIC INSTABILITY PHENOTYPE IN T-CELL LYMPHOMA

DE DIOS SOLER M; FUNDIA ARIELA F; SAPIA S; MARTIN C; LARRIPA IRENE; NARBAITZ M

Viena, Austria

Congreso; XIII Meeting of the European Association for Haematopathology; 2006

European Association for Haematopathology

Genomic instability caused by deficiency of mismatch repair genes (MMR) and revealed by microsatellite instability (MSI) has been observed in different solid tumors, but rarely in lymphomas. The aim of this study was to elucidate any possible association between MSI, MMR mutational status and T-cell lymphoma. A retrospective series of 21 lymph node biopsies from T-cell lymphomas were selected for the study. Immunohistochemistry was performed with primary anti-MLH1 and anti-MSH2 mouse monoclonal antibody. DNA was extracted from formalin?fixed paraffin-embedded blocks from patients and peripheral blood samples from 30 healthy individuals with phenol-chloroform. Mononucleotide microsatellites BAT-25 and BAT-26 were analyzed because they are frequently employed for MSI studies without the requirement for matching normal DNA. Amplification was performed in 25 µl with 0.2 µg genomic DNA, 1.5 mM MgCl2, 100 µM of each dNTP, 0,4µM of each primer and 1 unit Taq DNA polymerase. BAT 25 was amplified at 48 ºC and BAT 26 at 55ºC during 30 cycles. Electrophoresis was performed on 15 % non-denaturing polyacrylamide gels stained with silver nitrate (0.1%). MSI was scored according international criteria. STR allele genotyping on normal healthy individuals showed little allele variation demonstrating the quasi-monomorphic nature of these markers in Argentinean population. MSI was not detected in T-cell lymphoma cases. Absence of hMSH2 nuclear signal was detected in >70% of neoplastic cell in 2/21 cases and hMLH1 expression was also decreased in another 2 cases.  These results demonstrate that MSI is not a mechanism involved in the pathogenesis of T cell lymphoma.