engleski

Can alk expression discriminate anaplastic large cell lymphoma from variants of hodgkin's lymphoma?

Anaplastic Large Cell Lymphoma (ALCL) is described as a distinct clinico-pathological entity but recent studies suggest it to be a heterogeneous disorder. Pathomorphological similarities to some subtypes of Hodgkin’s Lymphoma (HL) contribute to such impression. Oncogenic marker, a fusion gene Nucleophosmin/Anaplastic Lymhoma Kinase (NPM/ALK) is reported to be specifically associated with ALCL. Resulting activity of a receptor tyrosine kinase ALK is considered responsible for lymphomagenesis. In a series of 121 consecutive CD30+ lymphoma patients, classified by experienced hematopathologist based on routine morphological and immunophenotypic analyses as either ALCL (49) or HL (72), ALK protein expression and incidence of NPM/ALK rearrangement was investigated to evaluate whether this marker has clinical prognostic power and whether adding ALK to other clinical and laboratory parameters will make a difference in discriminating ALCLs from HLs. ALK1+ immunostaining was found in 12/72 HLs and 13/49 ALCLs. Molecular analysis by RT-PCR in 46 available diagnostic lymph nodes revealed NPM-ALK fusion transcript in 2 ALCLs (1 also ALK1+) and 4 HDs. There is a discrepancy in the number of ALK1 immunoreactive cases and molecular results. However, molecular event of NPM-ALK rearrangement is not the only possible mechanism of ALK gene upregulation as more parter genes coming into fusion with ALK are being reported. On the other hand in six NPM-ALK gene positive but ALK protein negative cases a posttranslational modification of protein conformation might have impaired immunobinding properties of ALK1 antibody. Hematological and clinical characteristics were further compared in 111 patients (66 HL and 45 ALCL) where univariate analysis showed difference between the two groups for the presence of constitutional symptoms, performance status, ESR, WBC count, serum copper and LDH. There was no difference for the treatment modality, response, survival and DFS. ALK protein-positive patients, irrespective of lymphoma type, did not have better survival although in some previous reports ALK positivity conferred better prognosis. International Prognostic Index (IPI) has a significant prognostic power for ALCL with p=0.0440 among the 4 risk groups. In conclusion, our study found that evaluating ALK protein/gene expression did not show clinical prognostic value nor did it contribute to differentiation ALCLs from HD variants

lymphoma; alk; prognosis

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