Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes

Stathopoulos, E.; Sanidas, Elias; Kafousi, Maria; Mavroudis, Dimitris; Askoxylakis, John; Bozionelou, V.; Perraki, Maria; Tsiftsis, Dimitris D.; Georgoulias, Vassilis

doi:10.1093/annonc/mdi043

Cited by 53 publications

(37 citation statements)

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“…For instance, in a study of 47 patients without overt metastasis, all the patients with DTC in PB had micrometastasis in BM, whereas 36% of patients with micrometastasis in BM had no circulating cells in PB; there was no correlation between DTC in PB or BM and micro-metastasis in SLN (Zhu et al 2005). The absence of correlation between DTC in LN and DTC in PB has also been shown by other investigators (see the recent papers of Stathopoulos et al 2005, Wülfing et al 2006.…”

Section: Prognosis and Correlationsmentioning

confidence: 60%

“…Data indicating either the persistence or the disappearance of DTC after systemic treatment have been obtained (Braun et al 2000a, Smith et al 2000, Manhani et al 2001, Xenidis et al 2003, Bozionellou et al 2004, Hennessy et al 2005, Pachmann et al 2005, Pantel & Woelfle 2005, Slade et al 2005, Stathopoulos et al 2005, Drageset et al 2006, Quintela-Fandino et al 2006. Such discrepancies might reflect differences in the proliferation status of DTC or in the therapeutical agent used.…”

Section: Prognosis and Correlationsmentioning

confidence: 99%

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Significance, detection and markers of disseminated breast cancer cells

Lacroix¹

2006

Endocr Relat Cancer

258

220

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The development of distant metastases is the major cause of death from breast cancer. In order to predict and prevent tumour spreading, many attempts are being made to detect small numbers of tumour cells that have shed from the primary lesions and have moved to lymph nodes, blood or bone marrow. This article presents the advantages and the limitations of techniques used for disseminated tumour cells (DTC) detection. DTC markers are listed and the most currently used of them (KRT19, CEACAM5, TACSTD1, MUC1, EGFR, ERBB2, SCGB2A2, SCGB2A1, SCGB1D2, PIP, SBEM, TFF1, TFF3, ANKRD30A, SPDEF, ESR1, SERPINB5 and GABRP) are discussed, notably on the basis of recent data on breast tumour portraits (luminal epithelial-like, basal/myoepithelial-like and ERBB2). The significance of DTC for the prognosis and prediction of response to therapy is examined. DTC viability, the notion of cell dormancy and the concept of breast cancer stem cells are also discussed.

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Section: Prognosis and Correlationsmentioning

confidence: 60%

Section: Prognosis and Correlationsmentioning

confidence: 99%

Significance, detection and markers of disseminated breast cancer cells

Lacroix¹

2006

Endocr Relat Cancer

258

220

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“…To investigate further the significance of deregulated corepressor expression in breast cancer, we examined 21 matched tumor and normal breast cancer samples. To allow for epithelial enrichment in the tumor samples, the relative levels of corepressors were normalized to cytokeratin 19 mRNA, an established marker of mammary epithelial cells (39). There was considerable variation in the level of the VDR in both the ERapositive (14 of 21) and ERa-negative (7 of 21) tumors with a mean fold change of 4.9 F 2.1 and 11.8 F 7.3, respectively, compared with the matched normal, although there was significant variation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells

Banwell¹,

MacCartney²,

Guy

et al. 2006

Clinical Cancer Research

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Purpose:We hypothesized that deregulated corepressor actions, with associated histone deacetylation activity, epigenetically suppressed vitamin D receptor (VDR) responsiveness and drives resistance towards 1a,25-dihydroxyvitamin D 3 . Experimental Design: Profiling, transcriptional, and proliferation assays were undertaken in 1a,25(OH) 2 D 3 -sensitive MCF-12A nonmalignant breast epithelial cells, a panel of breast cancer cell lines, and a cohort of primary breast cancer tumors (n = 21). Results: Elevated NCoR1 mRNA levels correlated with suppressed regulation of VDR target genes and the ability of cells to undergo arrest in G 1 of the cell cycle. A similar increased ratio of corepressor mRNA to VDR occurred in matched primary tumor and normal cells, noticeably in estrogen receptor a^negative (n = 7) tumors. 1a,25(OH) 2 D 3 resistance in cancer cell lines was targeted by cotreatments with either 1a,25(OH) 2 D 3 or a metabolically stable analogue (RO-26-2198) in combination with either trichostatin A (TSA; histone deacetylation inhibitor) or 5-aza-2V-deoxycytidine (DNA methyltransferase inhibitor). Combinations of vitamin D 3 compounds with TSA restored VDR antiproliferative signaling (target gene regulation, cell cycle arrest, and antiproliferative effects in liquid culture) to levels which were indistinguishable from MCF-12A cells. Conclusions: Increased NCoR1 mRNA is a novel molecular lesion in breast cancer cells, which acts to suppress responsiveness of VDR target genes, resulting in 1a,25(OH) 2 D 3 resistance and seems to be particularly associated with estrogen receptor negativity.This lesion provides a novel molecular diagnostic and can be targeted by combinations of vitamin D 3 compounds and low doses of TSA.The nuclear receptor superfamily regulates diverse signals that are central to the formation and homeostasis of the mammary gland. The postgenomic description of the superfamily conjoined with profiling approaches (1) reveals that breast myoepithelial and epithelial cells express a rich cohort of nuclear receptors, many of which display overt nutrient-sensing capacity for micronutrients and macronutrients alongside the estrogen receptors (ERa and ERh; refs. 2 -6).Several of the diet-sensing nuclear receptors, such as the VDR, preferentially form heterodimers with retinoid X receptors whereas the ERs preferentially heterodimerize with one another. For the nuclear receptors to regulate transcriptional programs, these dimers must be contained as subunits in either large gene coactivator or corepressor complexes. In the absence of ligand, receptors exist in an apo state as part of large complexes (f2.0 MDa; ref. 7), associated with corepressors (e.g., NCoR1, NCoR2/SMRT, and TRIP15/Alien), and bound to response element sequences. These complexes actively recruit a range of enzymes that posttranslationally modify histone tails (e.g., histone deacetylases and methyltransferases) and thereby maintain a locally closed chromatin structure around response element sequences (8). Ligand binding induces a...

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“…Some groups have found that circulating tumor cells of inoperable breast cancer patients are associated with worse recurrence-free and overall survival (15)(16)(17). In contrast, others have reported that the presence of disseminated tumor cells is not convincingly associated with worse survival in operable breast cancer patients (8,18,19). In addition, the prognostic relevance of detection of disseminated tumor cells in the bone marrow of metastatic renal cell carcinoma patients has also been recently shown (20).…”

Section: Introductionmentioning

confidence: 99%

Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

Bluemke

Bilkenroth

Meye

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood (so-called circulating tumor cells) for renal cell carcinoma patients. Methods: Two hundred thirty-three peripheral blood samples from 154 renal cell carcinoma patients were investigated for the presence of disseminated tumor cells by autoMACS technique and immunocytochemical staining of cytokeratin. The frequency of circulating tumor cells was analyzed statistically for correlation with relevant clinical data. Results: Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+) and cells without a detectable cytokeratin expression, which we called large blue-stained cells with a tumorlike morphology. After following the CD45 autoMACS depletion protocol, we identified circulating tumor cells in 96 (41%) of 233 peripheral blood samples, which originated from 81 (53%) of 154 renal cell carcinoma patients.A significant correlation between the detection of circulating tumor cells and positive lymph node status (P < 0.001; χ 2 test) and the presence of synchronous metastases at the time of primary tumor resection (P = 0.014; χ 2 test) was found. In a multivariate Cox's regression hazard model, presence of CK+ circulating tumor cells was significantly correlated with poor overall survival for renal cell carcinoma patients (relative risk, 2.3; P = 0.048). Conclusions:The presence of circulating tumor cells correlated to lymph node status and presence of synchronous metastases in renal cell carcinoma. It is important to evaluate CK+ and blue-stained tumor cells together to determine the role of circulating tumor cells in tumor behavior and disease progression. Detection of CK+ circulating tumor cells in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2190-4)

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Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes

Abstract: Direct hematogenous dissemination of occult tumor cells may occur in a substantial proportion of patients with early-stage breast cancer. The prognostic implication of the detection of these cells requires long follow-up periods and further studies.

Cited by 53 publications

References 37 publications

Significance, detection and markers of disseminated breast cancer cells

Significance, detection and markers of disseminated breast cancer cells

Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells

Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

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