ANALYSIS OF BCL-2 IN SPORADIC BREAST-CARCINOMA

BACKGROUND. The bcl-2 gene encodes a protein that blocks apoptosis and might help to promote tumor development. It is expressed in a high pe rcentage of breast tumors and is associated with good prognostic featu res. However, the mechanisms that regulate bcl-2 expression in breast carcinoma are unknown. Moreover, immunohistochemical detection of bcl- 2 is related inversely to p53 expression. This notwithstanding, the im munohistochemical detection of p53 does not always correlate with the detection of p53 gene mutations. The authors studied the molecular org anization of bcl-2 as well as the methylation status of its CpG island and analyzed the correlation between bcl-2 expression and p53 gene mu tations. METHODS. The molecular organization of the bcl-2 gene and the methylation pattern of its CpG island were analyzed by Southern blot analysis. In addition, immunohistochemical analysis of bcl-2 and p53 p rotein expression was performed. Finally, the presence of mutations at exons 5-9 of the p53 gene were analyzed by polymerase chain reaction and single-strand conformation polymorphism. RESULTS. No molecular abn ormality was found at the bcl-2 locus in cases of sporadic breast carc inoma. Moreover, loss of heterozygosity analysis failed to detect any allelic loss in the study cases. It also was found that the bcl-2 CpG island was demethylated in all cases. These results point to a lack of correlation between bcl-2 protein expression and the presence of p53 gene mutations.CONCLUSIONS. The level of bcl-2 expression in breast ca rcinoma is not associated with any somatic abnormality or epigenetic c hange at the bcl-2 locus. Conversely, although bcl-2 expression is rel ated inversely to p53 protein expression, the analysis of p53 mutation s (limited to exons 5-9) failed to demonstrate any relationship betwee n p53 mutations and bcl-2 protein expression. (C) 1997 American Cancer Society.