Immunohistochemical Predictors of Bone Metastases in Breast Cancer Patients

Abstract

Bones are the most common metastatic site of relapse in breast cancer patients and the prediction of bone metastases (BM) risk might prompt developing preventive and therapeutic strategies. The aim of the study was to correlate immunohistochemical (IHC) expression of selected proteins in primary breast cancer with the occurrence of BM. We analyzed expression of proteins potentially associated with BM in primary tumors of 184 patients with metastatic breast cancer (113 with- and 71 without BM). Expression of estrogen receptor (ER) in primary tumor was more common in patients with- compared to those without BM (74 vs. 45 % respectively, p = 0.0001), whereas in this subset less common was expression of parathyroid hormone related protein receptor type 1 (16 vs. 34 %, respectively, p = 0.007) and cytoplasmic expression of osteopontin (OPNcyt; 1.9 vs. 14 %, respectively, p = 0.002). The relationship between expression of ER and OPNcyt and the occurrence of BM was confirmed in the multivariate analysis. The ER-positive/OPNcyt negative phenotype was significantly more common in patients with- compared to those without BM (75 and 25 %, p < 0.0001, respectively; HR 1.79, p = 0.013). Luminal A (43 vs. 23 % respectively, p = 0.009) and luminal B/HER2-positive (16 vs. 4.9 % respectively, p = 0.032) subtypes were more common in patients with- compared to those without BM, whereas triple negative breast cancer subtype was less common (16 vs. 38 %, p = 0.002).

Fig. 1

Representative images of particular proteins’ expression (magnification ×200). a CK 5/6, b CXCR4, c CaSR, d COX2, e OPN_n, f OPN_cyt, g PTHrPR1

Fig. 2

Overall survival of patients with bone metastases (n = 113) and with extraskeletal metastases (n = 71)

Fig. 3

Cumulative incidence of bone metastases in patients with ER-positive/OPN_cyt-negative immunohistochemical signature vs. others. Excluded were 16 patients in whom the assessment of either ER or OPN staining was not possible