Bcl-BExpression in Human Epithelial and Nonepithelial Malignancies

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 humanmalignancies 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 proteinwas strongly expressed in all normal plasma cells but found inonly18% 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 30%; ref. 12). Tissue microarrays (TMA) comprising paraffin-embedded lymph node specimens from 48 patients diagnosed with diffuse large B-cell lymphomas (DLBCL) and from 57 patients with follicular lymphoma were provided by the Robert H. Lurie Comprehensive Cancer Center, Northwestern University. Tumor specimens were obtained from 79 small cell lung cancer (SCLC) patients with limited disease who were treated by surgery followed by chemotherapy using various multidrug regimens at the Thoracic Surgery Department of Medical University of Gdansk between 1984 and 2001. In addition, thoracic radiation was given to 4% of the patients and prophylactic cranial irradiation to 8% of the patients. Patients ranged from clinical stages I to IIIA and were of good performance status (Karnofsky score, 80-100). Clinical data represent a median follow up of 1.3 y. TMAs containing specimens from 82 non-SCLC patients were obtained from Princess Margaret Hospital and Ontario Cancer Institute in Toronto. The specimens represented 22 adenocarcinomas, 32 squamous cell carcinomas, and 16 large cell carcinomas (12 unspecified