Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2

• Published in: Haematologica (Roma) Vol. 103; no. 7; pp. 1182 - 1190
• Main Authors: Horn, Heike, Kohler, Christian, Witzig, Raphael, Kreuz, Markus, Leich, Ellen, Klapper, Wolfram, Hummel, Michael, Loeffler, Markus, Trümper, Lorenz, Spang, Rainer, Rosenwald, Andreas, Ott, German
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.07.2018
• Subjects: Adult; Aged; Biomarkers, Tumor; Computational Biology - methods; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoma, Follicular - genetics; Lymphoma, Follicular - pathology; Male; Middle Aged; Neoplasm Grading; Transcriptome
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2017.181024

A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has been favored, since FL3A often co-exist with an FL1/2 component. FL3B, in contrast, is thought to be more closely related to diffuse large B-cell lymphoma (DLBCL), and both are often simultaneously present in one tumor (DLBCL/FL3B). To obtain more detailed insights into follicular lymphoma progression, a comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B (n=6), DLBCL/FL3B (n=9), and germinal center B-cell-type diffuse large B-cell lymphoma (n=45) was undertaken using gene expression profiling, immunohistochemical stainings and genetic analyses by fluorescence hybridization. While immunohistochemical (CD10, IRF4/MUM1, Ki67, BCL2, BCL6) and genetic profiles (translocations of BCL2, BCL6 and MYC) delineate FL1-3A from FL3B and DLBCL/FL3B, significant differences were observed between FL1/2 and FL3A upon gene expression profiling. Interestingly, FL3B turned out to be closely related to FL3A, not categorizing within a separate gene expression cluster, and both FL3A and FL3B showed overlapping profiles in between FL1/2 and diffuse large B-cell lymphoma. Finally, based upon their gene expression pattern, DLBCL/FL3B represent a composite form of FL3B and DLBCL, with the majority of samples more closely resembling the latter. The fact that gene expression profiling clearly separated FL1/2 from both FL3A and FL3B suggests a closer biological relationship between the latter. This notion, however, is in contrast to immunohistochemical and genetic profiles of the different histological FL subtypes that point to a closer relationship between FL1/2 and FL3A, and separates them from FL3B.