A summary of two clinical studies on tumor cell dissemination in primary and metastatic breast cancer: Methods, prognostic significance and implication for alternative treatment protocols (Review)

Kasimir‐Bauer, Sabine; Oberhoff, C.; Schindler, A. E.; Seeber, S.

doi:10.3892/ijo.20.5.1027

Cited by 12 publications

(11 citation statements)

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“…In our present study, CK+ cells in PB were detected in 62% of breast cancer patients when MNC and GC fractions were assessed. The overall CK+ rate reported in the present study is higher those published in previous studies 12, 13. Other studies, however, have reported higher or similar percentages of CK+ cells in PB then those showed in our present study.…”

Section: Discussionsupporting

confidence: 53%

Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen‐receptor status and predicts for poor prognosis

Gaforio

Serrano

Sánchez‐Rovira

et al. 2003

Intl Journal of Cancer

120

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We investigated whether detection of cytokeratin-positive (CK؉) cells in the peripheral blood (PB) of breast cancer patients before chemotherapy could be a prognostic factor. Blood from a total of 92 breast cancer patients was evaluated for the presence of CK؉ cells. Blood samples were collected before chemotherapy. Patients entered in the study included: neoadjuvant (n ‫؍‬ 25), adjuvant (n ‫؍‬ 42) and metastatic (n ‫؍‬ 25). Blood samples (10 ml) were centrifuged using a double density-gradient to recovering the mononuclear cell (MNC) and granulocyte cell (GC) fractions. Subsequently, positive immunomagnetic cell separation was carried out to isolating CK؉ cells. The enriched cell fraction was cytocentrifuged and then immunocytochemically labeled using an anti-cytokeratin antibody. Our results indicated that breast tumor cells sediment with both MNC and GC fractions. We showed that using the method we present, the detection of CK؉ cells in PB before starting the chemotherapy in breast cancer patients was significantly correlated with both progression-free survival (p ‫؍‬ 0.058) and overall survival (p ‫؍‬ 0.003). In conclusion, the present study suggests that detection of CK؉ cells in PB before chemotherapy might identify breast cancer patients with poor prognosis. Breast cancers have been shown to shed tumor cells into the circulation at the earliest stages of primary tumor development. It is accepted that it is the early hematogenous dissemination of the tumor that decides the patient's fate. Fehm et al. 1 have reported that circulating epithelial cells in breast cancer patients are malignant. The potential of circulating tumor cells to form metastases in vivo has been reported by Pretlow et al. 2 They showed the capacity to induce metastases in nude mice from tumor cells taken directly from the peripheral blood (PB) of patients. Thus, the early detection of circulating tumor cells may have important therapeutic and prognostic implications. It could be an independent prognostic factor that could identify the patients who are most likely to benefit from adjuvant therapy. Immunological and molecular methods have been used for detecting circulating tumor cells, 3 but it has not been possible to standardize a method internationally. This could explain the contradictory results obtained by different groups.We investigated whether detection of cytokeratin-positive (CKϩ) cells in PB of breast cancer patients before chemotherapy could be a prognostic factor. Cytokeratin is a valuable marker for breast tumor cell in PB. Blood from a total of 92 breast cancer patients was evaluated for the presence of CKϩ cells. Blood samples were collected before chemotherapy just when the patients were included in this study. Patients entered in the study included: neoadjuvant (n ϭ 25), adjuvant (n ϭ 42) and metastatic (n ϭ 25). Correlation of CKϩ cells with patient characteristics and with well established prognostic parameters were carried out. We have used an immunomagnetic separation procedure for the detection of circulating tumo...

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Section: Discussionsupporting

confidence: 53%

Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen‐receptor status and predicts for poor prognosis

Gaforio

Serrano

Sánchez‐Rovira

et al. 2003

Intl Journal of Cancer

120

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“…Detection of cytokeratin positive (CK+) cells from venous blood (sampling prior surgery, during mobilization of the liver on the bypass and after filter passage, 3×9 mL aliquots) was achieved after Ficoll® (Pharmacia, Germany) density gradient centrifugation (669 g, 4°C, 30 minutes) by immunohistochemical labelling with an anti-cytokeratin antibody and microscopic analysis, regarding cell-morphologic parameters (Epimet-kit®, Micromet, Germany) [16-18]. …”

Section: Methodsmentioning

confidence: 99%

Extracorporeal tumor cell filtration during extended liver surgery: first clinical use of leukocyte depletion filters – a case series

et al. 2013

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BackgroundDuring oncologic surgery, intraoperative manipulation of tumor tissue is almost unpreventable and causes a high risk of tumor cell dissemination into venous blood. A tumor cell-reducing effect of leukocyte adhesion filter systems has been shown under in vitro conditions.MethodsIn a first clinical attempt, leukocyte adhesion filters were integrated into veno-venous bypass systems in four patients undergoing extended liver surgery for secondary hepatic malignancies.Practicability, handling, and safety aspects as well as potency of cell removal and clinical side effects of the filter system were analyzed.ResultsAll patients tolerated the application of the system without problems during operative and postoperative follow-up. Immunohistochemical staining of perioperative blood samples detected cytokeratin positive (CK+) cells in three cases during the hepatic mobilization.ConclusionsEffectiveness of CK+ cell depletion and safety of the procedure was shown. The presented surgical technique represents a safe and innovative tool; however, clinical significance has to be examined in a larger patient cohort.

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“…After the cells had been air-dried overnight, staining for CK+ cells was performed with the Epimet kit (Micromet, Germany), based on the reactivity of the murine monoclonal antibody (Mab) A45-B/B3, directed against a common epitope of CK polypeptides [12]. The applied antibody A45-B/B3 for the detection of CK+ cells was shown to give no false-positive results as determined in a BM analysis of 165 patients without malignant diseases and is now commonly used [13].…”

Section: Preparation Of Bone Marrow and Blood Mononuclear Cells (Mncs)mentioning

confidence: 99%

Peri-operative filtration of disseminated cytokeratin positive cells in patients with colorectal liver metastasis

Frühauf¹,

Kasimir‐Bauer²,

Görlinger³

et al. 2004

Langenbecks Arch Surg

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A summary of two clinical studies on tumor cell dissemination in primary and metastatic breast cancer: Methods, prognostic significance and implication for alternative treatment protocols (Review)

Cited by 12 publications

References 0 publications

Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen‐receptor status and predicts for poor prognosis

Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen‐receptor status and predicts for poor prognosis

Extracorporeal tumor cell filtration during extended liver surgery: first clinical use of leukocyte depletion filters – a case series

Peri-operative filtration of disseminated cytokeratin positive cells in patients with colorectal liver metastasis

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