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Bcl-B Expression in Human Epithelial and Nonepithelial Malignancies

Authors' Affiliations: ¹ Burnham Institute for Medical Research, La Jolla, California; ² Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois; ³ Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California; ⁴ Unité Institut National de la Sante et de la Recherche Medicale U526, Faculté de Médecine, Nice, France; ⁵ Cancer Research Institute of M.D. Anderson Cancer Center Orlando, Orlando, Florida; ⁶ Yonsei University, College of Medicine; ⁷ Department of Pathology, Inje University Sanggyepaik Hospital, Seoul, South Korea; ⁸ Royal Victoria Eye and Ear Hospital; ⁹ St. Vincent's University Hospital; and School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College, Dublin, Ireland; ¹⁰ Aperio Technologies, Inc., Vista, California; ¹¹ Department of Oncology and Radiotherapy, Medical University of Gdask, Gdask, Poland; ¹² Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Kiel, Germany; ¹³ Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada; ¹⁴ Sidney Kimmel Cancer Center, San Diego, California; ¹⁵ M. D. Anderson Cancer Center, Houston, Texas; and ¹⁶ Department of Pathology and Laboratory Medicine, University California at Irvine, Irvine, California

Requests for reprints: John C. Reed, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037. Phone: 858-646-3140; Fax: 858-646-3194; E-mail: reedoffice{at}burnham.org.

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.