PMID- 16006802 OWN - NLM STAT- MEDLINE DCOM- 20050920 LR - 20220408 IS - 0147-5185 (Print) IS - 0147-5185 (Linking) VI - 29 IP - 8 DP - 2005 Aug TI - Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype". PG - 1067-73 AB - Amplification and translocation of the Bcl-2 gene has been detected in a certain subset of diffuse large B-cell lymphomas (DLBCL). The correlations among Bcl-2 protein expression, gene translocation or amplification, and the molecular signature determined by cDNA array are poorly understood. This study examined 25 cases with de novo nodal DLBCL. Interphase fluorescence in situ hybridization (FISH) analysis was performed to evaluate the Bcl-2 gene using IGH/BCL2 and CEP18 centromere probes (Vysis). When extra Bcl-2 gene signals were observed in each tumor cell and when these signals were in proportion to the extra CEP18 probe signals, we regarded the findings as indicating the presence of an additional chromosome 18; when extra Bcl-2 signals were observed but additional CEP18 signals were not, we regarded the findings as indicating the presence of gene amplification. A panel of 3 antigens (CD10, Bcl-6, and MUM-1) was applied to categorize each case as either a "germinal center B-cell (GCB) phenotype" or a "non-GCB phenotype." Of the 25 cases examined, 8 cases (32%) were classified as "GCB phenotype" and 17 cases (68%) were classified as "non-GCB phenotype." A FISH analysis revealed that t(14;18) was detected in 2 of the 8 cases (25%) with the "GCB phenotype" but in none of the 17 "non-GCB phenotype" cases. Extra Bcl-2 gene signals were detected in 7 of the 25 (28%) cases examined: n = 5 for an additional chromosome 18, n = 1 for gene amplification, and n = 1 for additional chromosome 18 + gene amplification. Extra Bcl-2 gene signals were exclusively detected in DLBCL with the "non-GCB phenotype"; these cases, with the exception of one, stained strongly positive for Bcl-2. The DLBCLs with Bcl-2 protein overexpression were classified into at least two heterogeneous molecular groups, based on the results of the FISH analysis. FAU - Kusumoto, Shigeru AU - Kusumoto S AD - Hematology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. FAU - Kobayashi, Yukio AU - Kobayashi Y FAU - Sekiguchi, Naohiro AU - Sekiguchi N FAU - Tanimoto, Kazuki AU - Tanimoto K FAU - Onishi, Yasushi AU - Onishi Y FAU - Yokota, Yukiko AU - Yokota Y FAU - Watanabe, Takashi AU - Watanabe T FAU - Maeshima, Akiko Miyagi AU - Maeshima AM FAU - Ishida, Takashi AU - Ishida T FAU - Inagaki, Hiroshi AU - Inagaki H FAU - Matsuno, Yoshihiro AU - Matsuno Y FAU - Ueda, Ryuzo AU - Ueda R FAU - Tobinai, Kensei AU - Tobinai K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Line, Tumor MH - Chromosomes, Human, Pair 14 MH - Chromosomes, Human, Pair 18 MH - Female MH - Gene Amplification MH - Genes, bcl-2/*physiology MH - Germinal Center/physiology MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lymphoma, B-Cell/*genetics/therapy MH - Lymphoma, Large B-Cell, Diffuse/*genetics/therapy MH - Male MH - Middle Aged EDAT- 2005/07/12 09:00 MHDA- 2005/09/21 09:00 CRDT- 2005/07/12 09:00 PHST- 2005/07/12 09:00 [pubmed] PHST- 2005/09/21 09:00 [medline] PHST- 2005/07/12 09:00 [entrez] AID - 00000478-200508000-00011 [pii] PST - ppublish SO - Am J Surg Pathol. 2005 Aug;29(8):1067-73.