Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases.
OBJECTIVE
Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents.


METHODS
The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53.


RESULTS
BCL-x protein was overexpressed in 18 of 42 (43%) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-xL was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL-x.


CONCLUSIONS
These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.
Olopade
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OI
Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago 60637-1470, USA.
Adeyanju
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Safa
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Hagos
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Mick
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Thompson
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Recant
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WM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D005260:Female; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein