Bcl-B expression in human epithelial and nonepithelial malignancies

Maryla Krajewska, Shinichi Kitada, Jane N. Winter, Daina Variakojis, Alan Lichtenstein, Dayong Zhai, Michael Cuddy, Xianshu Huang, Frederic Luciano, Cheryl H. Baker, Hoguen Kim, Eunah Shin, Susan Kennedy, Allen H. Olson, Andrzej Badzio, Jacek Jassem, Ivo Meinhold-Heerlein, Michaelj Duffy, Aaron D. Schimmer, Ming TsaoEwan Brown, Anne Sawyers, Michael Andreeff, Dan Mercola, Stan Krajewski, John C. Reed

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Purpose: Apoptosis plays an important role in neoplastic processes. Bcl-B is an antiapoptotic Bcl-2 family member, which is known to change its phenotype upon binding to Nur77/TR3. The expression pattern of this protein in human malignancies has not been reported. Experimental Design: We investigated Bcl-B expression in normal human tissues and several types of human epithelial and nonepithelial malignancy by immunohistochemistry, correlating results with tumor stage, histologic grade, and patient survival. Results: Bcl-B protein was strongly expressed in all normal plasma cells but found in only 18% of multiple myelomas (n = 133). Bcl-B immunostaining was also present in normal germinal center centroblasts and centrocytes and in approximately half of diffuse large B-cell lymphoma (n = 48) specimens, whereas follicular lymphomas (n = 57) did not contain Bcl-B. In breast (n = 119), prostate (n = 66), gastric (n = 180), and colorectal (n = 106) adenocarcinomas, as well as in non-small cell lung cancers (n = 82), tumor-specific overexpression of Bcl-B was observed. Bcl-B expression was associated with variables of poor prognosis, such as high tumor grade in breast cancer (P = 0.009), microsatellite stability (P = 0.0002), and left-sided anatomic location (P = 0.02) of colorectal cancers, as well as with greater incidence of death from prostate cancer (P = 0.005) and shorter survival of patients with small cell lung cancer (P = 0.009). Conversely, although overexpressed in many gastric cancers, Bcl-B tended to correlate with better outcome (P = 0.01) and more differentiated tumor histology (P < 0.0001). Conclusions: Tumor-specific alterations in Bcl-B expression may define subsets of nonepithelial and epithelial neoplasms with distinct clinical behaviors.

Original languageEnglish (US)
Pages (from-to)3011-3021
Number of pages11
JournalClinical Cancer Research
Volume14
Issue number10
DOIs
StatePublished - May 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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