The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19

Schoenfeld, Mircea Ariel; Krüger, Kjell; Gomm, Jennifer J.; Sinnett, H. D.; Gazet, J.‐C.; Sacks, N. P. M.; Bender, H. G.; Luqmani, Yunus A.; Coombes, R. Charles

doi:10.1016/s0959-8049(97)00014-2

Cited by 158 publications

(116 citation statements)

References 15 publications

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“…However, when a cutoff for positivity is established, the concordance between techniques was between 68 and 75%, meaning that although the sensitivity of techniques may be similar, the samples being called positive and negative are not necessarily the same. Other studies show qualitative concordance between PCR-based assays and immunocytochemistry of 71 -77% (Schoenfeld et al, 1997;Smith et al, 2000). In the case of the cytometric techniques, the limited concordance may reflect the differences in specimen handling.…”

Section: Discussionmentioning

confidence: 97%

“…These results show that when a multiple marker real-time RT -PCR assay is used, its sensitivity exceeds that of both an established and a novel cytometric technique. Previous studies using nonquantitative RT -PCR also reveal more positive results when patient samples are analysed by PCR than by immunocytochemical techniques (Schoenfeld et al, 1997;Lambrechts et al, 1999). However, these results may be compromised by lower specificity (Lambrechts et al, 1999).…”

Section: Discussionmentioning

confidence: 98%

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Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

et al. 2005

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This study compares the sensitivities and specificities of three techniques for the detection of circulating epithelial cells in the blood of patients with breast cancer. The number of circulating epithelial cells present in the blood of 40 patients with metastatic breast cancer and 20 healthy volunteers was determined by: immunomagnetic separation (IMS) and laser scanning cytometry (LSC), cell filtration and LSC and a multimarker real-time RT -PCR assay. Numbers of cytokeratin-positive cells identified and expression of three PCR markers were significantly higher in the blood of patients with breast cancer than in healthy volunteers. Using the upper 95% confidence interval of cells detected in controls to determine positive patient samples: 30% of patients with metastatic breast cancer were positive following cell filtration, 48% following IMS, and 60, 45 and 35% using real-time RT -PCR for cytokeratin 19, mammaglobin and prolactin-inducible peptide. Samples were significantly more likely to be positive for at least one PCR marker than by cell filtration (83 vs 30%, Po0.001) or IMS (83 vs 48%, Po0.001).The use of a multimarker real-time RT -PCR assay was therefore found to be the most sensitive technique for the detection of circulating epithelial cells in the blood of patients with breast cancer.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

et al. 2005

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“…Differences in the assays used could account for these discrepancies. Indeed, Schoenfeld et al (1997) have reported that the concordance between blood and bone marrow samples for occult tumour cell detection was only 6% by immunocytochemistry and 27% by RT-PCR. The lack of a complete overlap between the presence of CK-19 mRNA-positive CTCs and DTCs either before (Ismail et al, 2004;Pierga et al, 2004;Muller et al, 2005;Wiedswang et al, 2006) or after chemotherapy (Slade et al, 2009) could be related to the fact that occult tumour cells are rare events and therefore their evaluation is greatly influenced by sampling variability.…”

Section: Discussionmentioning

confidence: 99%

“…This is due to early tumour-cell dissemination through the lymphatic or the hematogenous vasculature (Dowlatshahi et al, 1997;Giatromanolaki et al, 2004;Stathopoulos et al, 2005). Indeed, epithelial tumour cells can be identified in bone marrow aspirates (disseminated tumour cells, DTCs) or in the peripheral blood (circulating tumour cells, CTCs) of otherwise metastases-free breast cancer patients using either immunohistochemical or molecular assays (Schoenfeld et al, 1997;Pantel et al, 1999;Slade et al, 1999).…”

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confidence: 99%

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

et al. 2009

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BACKGROUND: To compare detection rates and evaluate the clinical relevance of cytokeratin-19 (CK-19) mRNA-positive cells in the peripheral blood (circulating tumour cells, CTCs) and bone marrow (disseminated tumour cells; DTCs) of patients with early breast cancer. METHODS: Paired samples of peripheral blood and bone marrow were obtained from 165 patients with stage I -II breast cancer before the initiation of adjuvant chemotherapy. In 84 patients, paired blood and bone marrow samples were also available after chemotherapy. The detection of CK-19 mRNA-positive CTCs and DTCs was assessed by real-time PCR. RESULTS: CK-19 mRNA-positive CTCs and DTCs were detected in 55.2 and 57.6% of patients before chemotherapy, respectively. After chemotherapy, CTCs and DTCs were identified in 44 (52.4%) and 43 (51.2%) of the 84 patients, respectively. There was a 93.9% (McNemar; P ¼ 0.344) and 72.6% (McNemar; P ¼ 0.999) concordance between blood and bone marrow samples before and after chemotherapy, respectively. The detection of CK-19 mRNA-positive CTCs or DTCs before chemotherapy was associated with decreased overall survival (P ¼ 0.024 and P ¼ 0.015, respectively). In addition, their simultaneous detection was also associated with an increased incidence of disease-related death and decreased overall survival (P ¼ 0.016). CONCLUSIONS: The detection of CK-19 mRNA-positive CTCs using reverse transcription-PCR (RT -PCR) both before and after chemotherapy is correlated with the detection of CK-19 mRNA-positive DTCs in patients with early-stage breast cancer. The determination of the CTC status by RT -PCR conveys clinically relevant information that is not inferior to DTC status and, owing to the ease of sampling, warrants further evaluation as a tool for monitoring minimal residual disease.

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“…On account of the difficulties inherent in subjecting patients to regular bone marrows, as well as the small number of cells detected in primary patients with no evidence of overt metastases, such tests have been difficult to apply in routine clinical practice. Furthermore, until recently, the peripheral blood has been shown to be generally negative for CTCs in all but a minority of patients, with most series showing 1 -5% of patients found to be positive (Schoenfeld et al, 1997;Slade et al, 2005).…”

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confidence: 99%

Comparison of bone marrow, disseminated tumour cells and blood-circulating tumour cells in breast cancer patients after primary treatment

Slade¹,

Payne²,

Riethdorf

et al. 2008

Br J Cancer

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The purpose of this study was to determine whether primary breast cancer patients showed evidence of circulating tumour cells (CTCs) during follow-up as an alternative to monitoring disseminated bone marrow tumour cells (DTCs) by immunocytochemistry and reverse transcriptase (RT) -PCR for the detection of micrometastases. We planned to compare CTC and DTC frequency in low-risk and high-risk patients. We identified two cohorts of primary breast cancer patients who were at low (group II, T 1 N 0 , n ¼ 18) or high (group III, 43 nodes positive (with one exception, a patient with two positive nodes) n ¼ 33) risk of relapse who were being followed up after primary treatment. We tested each cohort for CTCs using the CellSearch system on 1 -7 occasions and for DTCs by immunocytochemistry and RT -PCR on 1 -2 occasions over a period of 2 years. We also examined patients with confirmed metastatic disease (group IV, n ¼ 12) and 21 control healthy volunteers for CTCs (group I). All group I samples were negative for CTCs. In contrast, 7 out of 18 (39%) group II primary patients and 23 out of 33 (70%) group III patients were positive for CTCs (P ¼ 0.042). If we count only samples with 41 cell as positive: 2 out of 18 (11%) group II patients were positive compared with 10 out of 33 (30%) in group III (P ¼ 0.174). In the case of DTCs, 1 out of 13 (8%) group II patients were positive compared with 19 out of 27 (70%) in group III (Po0.001). Only 10 out of 33 (30%) patients in group III showed no evidence of CTCs in all tests over the period of testing, compared with 11 out of 18 (61%) in group II (P ¼ 0.033). A significant proportion of poor prognosis primary breast cancer patients (group III) have evidence of CTCs on follow-up. Many also have evidence of DTCs, which are more often found in patients who were lymph node positive. As repeat sampling of peripheral blood is more acceptable to patients, the measurement of CTCs warrants further investigation because it enables blood samples to be taken more frequently, thus possibly enabling clinicians to have prior warning of impending overt metastatic disease.

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The detection of micrometastases in the peripheral blood and bone marrow of patients with breast cancer using immunohistochemistry and reverse transcriptase polymerase chain reaction for keratin 19

Cited by 158 publications

References 15 publications

Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

Comparison of bone marrow, disseminated tumour cells and blood-circulating tumour cells in breast cancer patients after primary treatment

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