P4-16-06: Expression Patterns of Receptor Activator of Nuclear Factor-kB (RANK) and Src in a Series of Primary Breast Tumors (BT) and Bone Metastases (BM) in Patients (pts) with Metastatic Breast Cancer (MBC).

Abstract

Abstract Background BM develops in 65–70% of pts with MBC. RANK and its ligand (RANK-L) can be critical in the development and progression of BM. Src overexpression and deregulation occurs in many solid tumors but it has not been fully characterized although an association between Src activity defined by a gene expression signature and BM particularly in ER+ pts has been described. (Zhang XH et al. Cancer Cell. 2009) Our goal was to elucidate the relationship between Src and RANK expression in BT and BM in relation to estrogen-/progesterone-receptor (ER/PR)/HER2 expression and tumor histology (invasive ductal carcinoma (IDC) vs invasive lobular carcinoma (ILC)). Methods: Immunohistochemistry (IHC) for RANK (R&D Systems clone 80707) and Src (Cell Applications Inc. Phospho Tyr-416) protein expression was performed on archived paraffin embedded BT and BM. Scoring: 0=negative, 1+=weak, 2+=intermediate, 3+=strong and the percent of positive tumor cells; RANK+ = 2–3+, > 1% of cells; Src+ = 1–3+; > 1% of cells. Associations between RANK/Src expression and tumor characteristics were assessed using the chi-square test or McNemar's test for pairs, as appropriate. Results: From the MSKCC database, using an IRB-approved waiver of consent, we identified 54 pts with MBC who underwent surgical biopsy of a metastatic bone lesion at our center between 2005–2010, and had tissue available for further testing. 17 corresponding BT samples were identified. At the time of diagnosis, 43 (79.5%) primary tumors were ER or PR (+); 6 (11%) were HER2+; 41 (76%) were invasive ductal carcinoma. 87% of BM expressed RANK and 44% expressed Src. (Table 1) No significant correlation between RANK or Src expression in BM and ER/PR/HER2 status of BT was observed. A significant correlation between RANK expression and BT histology was observed, (p=0.0016): 93% of IDC were RANK (+), in comparison to 50% of invasive lobular carcinomas. RANK expression was not significantly different between primary tumor and metastatic bone samples (p=0.99). There was a borderline significant difference in Src expression between primary and metastatic site (p=.06). Conclusions: In our cohort, no correlation between RANK or Src by IHC and ER/PR/HER2 was identified but RANK expression was more common in IDC than ILC. Fidelity was high for RANK between primary and metastatic lesions while Src expression may possibly vary. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-06.