Evaluation of cell line-derived xenografted tumors as controls for immunohistochemical testing for estrogen receptors and progesterone receptors

Abstract

Current Quality Control (QC) practices for diagnostic immunohistochemistry (IHC) use archived breast cancer specimens and breast cancer cell lines as control materials for Estrogen Receptor (ER) and Progesterone Receptor (PR) testing in breast cancer. However, archived breast tumors show inherent heterogeneity within and between specimens and cell lines are not histologically representative of patient-derivedtumor controls. In an effort to generate standardized controls for ER and PR IHC testing, I hypothesized breast cancer cell line-derived xenografted tumors are representative of patient-derived-tumor controls that can be used for QC purposes. Well-characterized breast cancer cell lines with varying steady-state levels of ER and PR expression – MCF7, T47D and MDAMB468 – analyzed by immunoblot and IHC were implanted in immune-deficient mice to generate cell line-derived Xenografted (CDX) tumors. ER and PR expression of the Xenografted tumors was consistent with the derivative cell lines. Three pathologists expert in breast biomarker reporting assessed CDX tumors for reproducibility from different Mammary Fat Pad (MFP) sites in the mice. The CDX tumors were indistinguishable regardless of the MFP sites. The xenografted tumors from the three cell lines represented the range of biomarker expression levels exhibited by the patient-derived-tumor controls. These results suggest the possible potential applications of CDX tumor as controls to assist in reporting of ER and PR test results.