Proliferative fraction, bcl-1 gene translocation, and p53 mutation status as markers in mantle cell lymphoma

The molecular genetic hallmark of mantle cell lymphomas (MCL) is the recipr ocal translocation t(11;14) (q13;q32) which juxtaposes the bcl-1 proto-onco gene to one of the joining segments of the immunoglobulin heavy chain gene. This translocation is very common in MCL and occurs in up to 70% of these malignancies. Due to the aggressive nature of MCL, markers identifying tumo r progression and clinical outcomes are necessary. In this study we examine d whether a corroborative relation exists between p53 mutations, bcl-1 tran slocation, and the proliferative fraction in MCL. We evaluated the prolifer ative fraction, p53 gene status, and bcl-1 translocation in 21 patients wit h confirmed MCL. Controls consisted of normal DNA and 7 B-cell lymphomas. I mmunohistochemical detection of Ki-67 was used to assess proliferative acti vity while molecular techniques were used to detect p53 mutations and the b cl-1 gene translocation. Reactivity to the monoclonal antibody Ki-67 on neo plastic cells ranged from 5% to 40% in typical MCL cases. The bcl-1 gene tr anslocation was detected by PCR in 48% (10/21) of MCLs while no rearrangeme nts were detected by PCR in case control DNA. Screening exons 5-8 of the p5 3 gene for mutations did not identify a single mutation in any of the MCL c ases. No correlation was found between p53 mutations, the presence of a bcl -1 translocation, and the proliferative activity of neoplastic MCL cells. W e conclude that these markers may demonstrate independent events which occu r during the pathogenesis of MCL.