c-myc, p53 and bcl-2, apoptosis-related genes in infiltrating breast carcinomas: Evidence of a link between bcl-2 protein over-expression and a lower risk of metastasis and death in operable patients
✍ Scribed by Monique G. Lê; Marie-Christine Mathieu; Setha Douc-Rasy; Marie-Luce Le Bihan; Howayda Adb El All; Marc Spielmann; Guy Riou
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 104 KB
- Volume
- 84
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Apoptosis is an important physiological process controlled by multiple genes, including c-myc, p53 and bcl-2, and its inhibition may lead to the development of human cancers. In this study, we analyzed expression of the c-myc gene using Northern blot and of the p53 and bcl-2 proteins by immunohistochemistry in 175 breast tumor specimens obtained from patients with operable breast cancer. We evaluated the relation between expression of these 3 genes and (i) the main usual prognostic factors (tumor size, histo-prognostic grade, hormone receptors and number of positive nodes); (ii) the risk of death and relapse, taking into account these 4 factors, after a mean period of follow-up of 9.5 years (SD 2 years). Over-expression of c-myc, p53 and bcl-2 was observed in 35%, 23% and 63% of tumors, respectively. Over-expression of c-myc was strongly linked to the number of positive nodes (p ؍ 0.0005). p53 protein expression was associated with both high-grade (p ؍ 0.0001) and hormone receptor-negative (p ؍ 0.0001) tumors. In contrast, bcl-2 protein over-expression was associated with the main favorable prognostic factors and, more particularly, with hormone receptor-positive tumors (p ؍ 0.0001). Multivariate analysis, using the Cox model, showed that only 2 factors were independently linked to the risk of death: number of positive nodes, which increased the risk (p ؍ 0.0001), and bcl-2 protein overexpression, which decreased the risk (p ؍ 0.008). When bcl-2 over-expression was studied in relation to nodal status, hormone receptor status and chemo-and hormone therapy, no significant difference was observed between different subgroups of patients. bcl-2 expression was also associated with a significantly lower risk of distant metastasis (p ؍ 0.04). In conclusion, bcl-2 expression characterizes a particular phenotype of breast cancer with a favorable prognosis, and it may therefore be used as a marker of long-term survival. Int.