title: Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype.
abstract: Primary breast diffuse large B-cell lymphoma has a poor prognosis relative to other extranodal diffuse large B-cell lymphoma. Recently, diffuse large B-cell lymphoma has been subclassified as germinal center B-cell-like and nongerminal center B-cell types using tissue microarrays. The 5-year overall survival rate of the germinal center B-cell group is better than that of the nongerminal center B-cell group. To elucidate the reason for which primary breast diffuse large B-cell lymphoma has a poor clinical outcome, we investigated 15 patients with primary breast diffuse large B-cell lymphoma (stage IE; 13 cases, stage IIE; two cases) by immunohistochemistry using various markers including CD10, Bcl-6, MUM1 and MIB-1 and by molecular analysis of the immunoglobulin heavy chain gene variable region. Immunohistochemistry showed 0/15 (positive cases/examined cases) for CD10, 5/15 for Bcl-6, 15/15 for MUM1, 10/15 for Bcl-2, 2/15 for CD5 and 4/15 for CD40. The expression pattern of CD10(-) MUM1(+) in primary breast diffuse large B-cell lymphoma corresponded to the nongerminal center B-cell group. Moreover, the MIB-1 index was distributed from 60 to 95% with a mean of 79%, indicating a high proliferation of the lymphoma cells. The immunoglobulin heavy chain gene variable region of primary breast diffuse large B-cell lymphoma had a mutation frequency of 1-10% (seven cases) and 0-1 additional mutations in ongoing mutation analysis (five cases). Primary breast diffuse large B-cell lymphoma had characteristics of the nongerminal center B-cell group. In conclusion, primary breast diffuse large B-cell lymphoma has a nongerminal center B-cell phenotype and has a high MIB-1 index. These features might therefore be associated with poor prognosis.
authors.affiliation: Second Department of Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. ysayaka@fmu.ac.jp
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yoshida
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yasuda
authors.forename: Hiroya
authors.initials: H
authors.lastname: Sagara
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohtake
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Abe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019013:CD40 Antigens / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors; D019394:Ki-67 Antigen / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000032:analysis; D000099218:Interferon Regulatory Factor-4
chemical_list: D018951:Antigens, CD20; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D050835:Interferon Regulatory Factors; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4