Genetisches Rearrangement und Proteinexpression des Proto-Onkogens Bcl6 sind mit der blastischen Transformation des extranodalen Marginalzonen-B-Zell-Lymphoms vom MALT-Typ assoziiert

Abstract

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a low-malignant non-Hodgkin B-cell lymphoma which is often localized in the gastrointestinal tract. It is characterized by a small cell morphology. The simultaneous existence of MALT lymphoma and large B-cell lymphoma is defined as a composite lymphoma (ComL). As previously shown, large B cell lymphomas in the gastrointestinal tract have almost always developed out of MALT lymphoma and therefore can be called blastic marginal zone B-cell lymphoma (blastic MZBL). In this dissertation, a panel of seven MALT lymphomas, eight ComL and thirteen blastic MZBL has been analyzed using fluorescence in-situ hybridization (FISH) for the detection of rearrangements of IGH, MALT1, BCL6, BCL10 and FOXP1 and immunohistochemistry for Bcl6, Bcl10 and FoxP1. Merely one large cell component of a ComL showed the translocation IGH-BCL10. This probe also showed the strongest staining intensity for Bcl10 immunohistochemistry, although the number of cells expressing this protein was below 30 %. No FOXP1 rearrangement was found in any of the cases, whereas FoxP1 expression was found in several cases, especially in the blastic cell populations. Genetic rearrangements of BCL6 were found more often in the blastic MZBL and the large-cell components of ComL than in the MALT lymphomas and the small-cell components of ComL (33 % vs. 9 %, p=0,2093). On the other hand, Bcl6 protein expression was found exclusively in the blastic MZBL and the large-cell components of ComL (p=0.0261). These results indicate that Bcl6 can be regarded as a marker for the malignant transformation of MALT lymphoma.