Abstract P2-01-10: Immunocytochemistry staining for estrogen and progesterone receptor in circulating tumor cells: Concordance between primary and metastatic tumors.

Abstract

Introduction: Estrogen (ER) and progesterone receptor (PR)) status is recommended by immunohistochemistry (IHC) and is considered standard practice for selection of treatment options in all breast cancer patients. Because biopsy is not often feasible in every patient presenting with recurrent and/or metastatic disease, circulating tumor cells (CTCs) offer an attractive alternative source of tumor tissue for determining ER/PR status. In addition, CTCs enable monitoring for more effective course of treatment. Experimental Design: Twenty ml of peripheral blood was collected prospectively from 34 patients diagnosed with late stage metastatic/recurrent breast cancer. CTCs were isolated using the microfluidic OncoCEE platform. A cocktail of antibodies was utilized for CTC capture, and detection was accomplished with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on CK+/CD45- CTCs captured directly within the microchannel and then compared to IHC performed on the primary and/or metastatic tumor. Results: CK+/CD45−/DAPI+ cells were detected in 22 of 34 (65%) patients with late stage breast cancer and assessed for ER/PR immunocytochemistry. Among the 22 cases with one or more CTCs, a concordance of 75% (15/20) and 90% (9/10) in ER/PR status between primary and metastatic tumor was observed, respectively. An overall concordance of 86% (19/22) was achieved. Five cases were discordant based on primary tissue alone; however, two of these cases are concordant when compared to the metastatic biopsy. Thus, only three cases were found to be discordant: all three were positive by IHC on the primary and/or metastatic tumor but negative by CTCs and all three had relatively low numbers of CTCs detected. Conclusions: There is significant heterogeneity of ER/PR protein expression in CTCs and primary/metastatic tumor biopsy. In addition, hormonal status may change over time due to therapy. ER/PR ICC on CTCs using the OncoCEE platform is shown to be feasible, with high concordance (86%) as compared to primary and/or metastatic biopsy (by IHC). The significance of heterogeneity at the ER/PR protein level in CTCs related to the prognosis and predictive response to anti-estrogen therapy needs further evaluation in larger prospective clinical trials. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-10.