Comparison of Predictive Immunohistochemical Marker Expression of Primary Breast Cancer and Paired Distant Metastasis using Surgical Material

Abstract

Parallel studies of primary breast carcinomas and corresponding distant metastases samples reveal considerable differences. Our aim was to highlight this issue from another perspective and provide further data based on 98 patient samples: 69 primary breast carcinoma and 85 distant metastases from bone, central nervous system (CNS) and lung (56 paired). Two independent series of immunohistochemical reactions with different antibodies for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (Her2), along with HER2 fluroscence in situ hybridization (FISH) were performed on tissue microarrays to classify breast carcinoma and distant metastases samples into Luminal A, Luminal B-proliferating, Luminal B-HER2+, HER2+ and triple negative (TNBC) surrogate breast cancer groups. Correlation and agreement between the two assessments of ER and PgR were fair-to-moderate, and almost perfect for HER2 and Ki67. There was 40% discordance concerning immunophenotype between breast carcinomas and distant metastases. Most common metastatic site of ER+ breast carcinoma was the skeletal system (59.2%), whereas that of TNBCs was the CNS (58.8%) and lungs (23.5%). Distant metastases in bones were mostly luminal (54.3%), in the CNS, Luminal B (53.2%), and in the lung, TNBC (37.5%). The change of drugable properties of primary breast cancers in the respective bone and CNS metastases suggests that characterization of the metastasis is necessary for appropriate treatment planning.

Discordance of the estrogen receptor and HER-2/neu in breast cancer from primary lesion to first and second metastatic site

“…We and others have previously shown a substantial discordance rate between primary tumor and metastatic disease, with studies reporting hormone receptor discordance rates between 30% and 40% and HER-2/neu discordance rates between 10% and 30%. 1 , 3 , 4 , 8 – 10 Although the American College of Pathologists recommends biomarker analysis on primary and metastatic breast cancers, 13 to the authors’ knowledge this is the first report which analyzes the continued biomarker discordance of primary breast cancer with paired specimens of first and subsequent metastases. Our current study examined the markers on paired samples from subsequent sites of metastasis.…”

“…Discordance between primary and metastatic breast cancer has been suggested for many years; however, most studies were retrospective, with only a few prospective studies now reporting biomarker discordance rates. 8 , 9 …”

The Hidden Story on Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma – Association with Clinical Outcome and Tumor Phenotypes

“…morphology, tumor mutational burden, and eventually BRAF status [46,47]. At the time of the actual treatment, the latest information source is key to the optimal choice of therapy, thus, metastases shall be sampled and analyzed at time of progression [48,49]. Our study therefore further extends the existing knowledge on the role played by the BRAF V600E mutation in malignant melanoma.…”

Immunohistochemical evaluation of bone metastases

“…An explanation to this may be the fact that metastatic tumors can change geno-or phenotype. Hence, different immunoprofiles of primary carcinomas and their metastasis may exist [15]. On the other hand, carcinomas of the unknown primary site represent, by themselves, a separate clinical entity that accounts for about 5% of all cancers [16].…”