Bcl-B expression in human epithelial and nonepithelial malignancies.
OBJECTIVE
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.


METHODS
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.
Krajewska
Maryla
M
Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Kitada
Shinichi
S
Winter
Jane N
JN
Variakojis
Daina
D
Lichtenstein
Alan
A
Zhai
Dayong
D
Cuddy
Michael
M
Huang
Xianshu
X
Luciano
Frederic
F
Baker
Cheryl H
CH
Kim
Hoguen
H
Shin
Eunah
E
Kennedy
Susan
S
Olson
Allen H
AH
Badzio
Andrzej
A
Jassem
Jacek
J
Meinhold-Heerlein
Ivo
I
Duffy
Michael J
MJ
Schimmer
Aaron D
AD
Tsao
Ming
M
Brown
Ewan
E
Sawyers
Anne
A
Andreeff
Michael
M
Mercola
Dan
D
Krajewski
Stan
S
Reed
John C
JC
D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D014162:Transfection
C117144:BCL2-like 10 protein; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2