β2M expression was positively correlated with p-CREB, p-SGK1, and Bcl-2 expression and had no correlation with HIF-1α, VEGF, and p-ERK1/2, whereas p-SGK1 exhibited a significantly positive correlation with Bcl-2 expression in cancer tissues of patients with luminal A breast cancer, which coincide with the results obtained from the same molecular types of breast cancer cells except CREB signaling.
This comparison showed that immunohistochemical bio-profiles select those cases not associated with high risk-of-recurrence of disease (luminal-A/B and luminal A/B Bcl2) and those that are instead at high risk and therefore worthy of chemotherapy (luminal-B ki67 and luminal-B Bcl2/Ki67), strongly suggesting to only submit PGR-positive/Bcl2-Ki67 altered cases to Oncotype Dx, thus reducing the number of cases to be tested.
Investigation of antiapoptotic Bcl-2 family members in clinical breast cancer datasets revealed greater expression and more frequent gene amplification of <i>MCL1</i> as compared with <i>BCL2</i> or <i>BCL2L1</i> (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like.
The findings of less aggressive luminal A and B subtypes in older patients, and the positive correlation with ER, PR and Bcl-2 expression reveal the potential efficacy of Bcl-2 as a marker of hormone responsiveness in these patients.
Not all PR low luminal A cases had poorer outcome compared to the PR high luminal A cases; poor prognosis was only limited to those with also low Bcl2 (log-rank = 23.568, P < 0.001 compared to PR high Bcl2 high cases).
The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000).