Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology

Lau, Sean K.; Frankel, Paul; Hsieh, H. C.; Liu, Xiaohe; Yang, Lixin; Krivacic, Robert T.; Bruce, Richard H.

doi:10.1007/s10549-011-1508-0

Cited by 115 publications

(80 citation statements)

References 48 publications

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“…Moreover, we observed virtually no concordance between positivity for ERCC1 transcript expression in CTC and ERCC1 protein expression in corresponding primary tumor tissue. This finding is corroborated by a recent study on advanced breast cancer, in which poor correlation between ERCC1 protein expression in CTC vs primary tumor was reported (37 ). These findings indicate that ERCC1 protein and ERCC1 transcript detection in these 2 compartments may capture "orthogonal" snapshots due to the different biological behavior of primary tumor vs blood-derived tumor cells and may provide complementary and independent clinical information on prognosis and platinum sensitivity.…”

Section: Discussionsupporting

confidence: 77%

ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

et al. 2014

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BACKGROUND Platinum resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Notably, the detection of the primary tumor-based excision repair cross-complementation group 1 (ERCC1) protein by immunohistochemistry was recently shown to be inaccurate for the prediction of platinum resistance. On the basis of the previous finding that circulating tumor cells (CTC) in the blood of ovarian cancer patients are prognostically significant, and given our hypothesis that the negative prognostic impact of CTC may arise from a cellular phenotype associated with platinum resistance, we asked whether expression of the excision repair cross-complementation group 1 (ERCC1) gene in the form of the ERCC1 transcript in CTC may be a suitable blood-based biomarker for platinum resistance. METHODS The presence of CTC was analyzed by immunomagnetic CTC enrichment (n = 143 patients) targeting the epithelial epitopes epithelial cell adhesion molecule (EPCAM) (also known as GA733-2) and mucin 1, cell surface associated (MUC1), followed by multiplex reverse-transcription PCR to detect the transcripts EPCAM, MUC1, and mucin 16, cell surface associated (MUC16) (also known as CA125), including ERCC1 transcripts in a separate approach. ERCC1 expression in primary tumors was comparatively assessed by immunohistochemistry, using the antibody 8F1. RESULTS At primary diagnosis, the presence of CTC was observed in 14% of patients and constituted an independent predictor of overall survival (OS) (P = 0.041). ERCC1-positive CTC (ERCC1+CTC) were observed in 8% of patients and constituted an independent predictor, not only for OS but also for progression-free survival (PFS) (P = 0.026 and P = 0.009, respectively). More interestingly, we discovered the presence of ERCC1+CTC at primary diagnosis to be likewise an independent predictor of platinum resistance (P = 0.010), whereas ERCC1 expression in corresponding primary tumor tissue predicted neither platinum resistance nor prognosis. CONCLUSIONS The presence of ERCC1+CTC can serve as a blood-based diagnostic biomarker for predicting platinum resistance at primary diagnosis of ovarian cancer.

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Section: Discussionsupporting

confidence: 77%

ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

et al. 2014

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“…Currently, therapeutic decisions are mainly based on primary tumor markers. However, several studies have shown a high degree of discordance between the primary tumor and metastatic sites or CTCs with respect to hormone receptor and HER2 expression (40)(41)(42)(43). Given the estimated short life span of CTCs in the circulation (44), the presence of CTCs in the peripheral blood of breast cancer patients after primary tumor resection suggests that the pool of CTCs is replenished by occult micrometastases.…”

Section: Discussionmentioning

confidence: 99%

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Janni

Rack

Terstappen

et al. 2016

Clinical Cancer Research

330

234

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Purpose: Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTC) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis.Experimental Design: We conducted a pooled analysis of individual data from 3,173 patients with nonmetastatic (stage I-III) breast cancer from five breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the FDA-cleared CellSearch System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months.Results: One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histologic tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histologic tumor grade, and hormone receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival [HR, 1.82; 95% confidence interval (CI), 1.47-2.26], distant disease-free survival (HR, 1.89; 95% CI, 1.49-2.40), breast cancer-specific survival (HR, 2.04; 95% CI, 1.52-2.75), and overall survival (HR, 1.97; 95% CI, 1.51-2.59).

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“…Because enrichment steps may lead to a bias in the selection of CTCs, high-speed automated digital microscopy using fiber-optic array scanning technology has been developed to detect CTCs that have been labeled by antibodies with fluorescent conjugates (15 ). Other slide-based automated scanning microscopes have been introduced for detecting CTCs, but the promising results still must be validated in large clinical studies (16 ).…”

Section: Protein-based Strategiesmentioning

confidence: 99%

Circulating Tumor Cells: Liquid Biopsy of Cancer

2013

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BACKGROUND:The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with Ͼ400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients.CONTENT: This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecularcharacterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelialmesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells).

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Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology

Cited by 115 publications

References 48 publications

ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

Circulating Tumor Cells: Liquid Biopsy of Cancer

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