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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 40 (2000), S. 681-687 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Immunzytologie ; Disseminierte epitheliale Zellen im Knochenmark ; Mammakarzinom ; Molekularbiologische Methoden ; PCR-Technik ; Keywords Immunocytochemistry ; Disseminated epithelial cells of bone marrow ; Primary breast cancer ; Molecular biological methods ; PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. The immunocytological detection of disseminated epithelial cells in bone marrow in patients with breast cancer has been performed at many hospitals and institutes since the early 1980s. Despite numerous publications in this field, it has not been possible to standardize the method and establish the ideal antibody, either nationally or internationally. Molecular biological methods using PCR technology could extend the diagnostic spectrum. However, one of the major problems in breast cancer is the lack of a disease-specific marker gene. As a result, immunocytology is still the standard procedure for tumour cell detection. Methods. The detection of disseminated single cells in bone marrow in primary breast cancer (also known as minimal residual disease) is a new prognostic factor for disease-free and overall survival. This has been demonstrated in three large (N〉300) groups and several small to medium groups (N=50–300). As a marker of dissemination in a target organ for metastasis this prognostic factor corresponds much more closely to the tendency of breast cancer to early haematogenic spread. Tumour cell detection may predict the course of the disease better than the axillary lymph node status. Bone marrow aspiration and detection of disseminated cells might replace lymph node dissection, at least in those patients with small tumours and no clinical signs of lymph node involvement. This strategy will soon be investigated in appropriate studies. Another possible clinical use might be deciding on whether or not to give adjuvant systemic therapy to node-negative patients. Patients with positive tumour cell detection are at a higher risk of subsequent metastasis, even if the axillary nodes are histologically normal. Application of methods. The immunohistological or molecular biological detection of tumour cells in axillary lymph nodes might also be very useful, now that is has been shown that a considerable subset of patients determined to be node-negative by means of conventional methods, are positive according to these new techniques. These methods could be a useful supplement to sentinel node biopsy. A further potential use of this method is in monitoring therapy with new treatment modalities such as gene therapy and immunotherapy. Repeated bone marrow aspiration can provide information on the success of therapy in minimal residual disease (cytoreduction). Immunocytochemical investigation of individual cells may be useful in studying the pathogenesis of metastasis, in particular in the skeleton. Phenotyping of cells might allow statements to be made in the metastatic potential of cells and the question of cell dormancy. It remains to be hoped that this aspect of minimal residual disease will be granted more attention in future.
    Notes: Zusammenfassung Hintergrund. Der immunzytologische Nachweis disseminierter epithelialer Zellen im Knochenmark bei Patientinnen mit Mammakarzinom wird seit den frühen 80er Jahren in vielen Kliniken und Institutionen durchgeführt. Trotz zahlreicher Publikationen zum Thema ist es bis heute weder national noch international gelungen, die Methode zu standardisieren und den “idealen” Antikörper zu etablieren. Methoden. Molekularbiologische Methoden mit der PCR-Technik könnten eine Erweiterung des diagnostischen Spektrums darstellen. Derzeit bleibt die Immunzytologie das Standardverfahren zum Tumorzellnachweis. Anwendungsmöglichkeiten. Der Nachweis disseminierter Einzelzellen im Knochenmark beim primären Mammakarzinom ist ein neuer unabhängiger Prognosefaktor für das krankheitsfreie und Gesamtüberleben und könnte von Nutzen bei der Entscheidungshilfe zur adjuvanten Systemtherapie bei nodalnegativen Patientinnen sein. Eine weitere Einsatzmöglichkeit der Methode ist die Therapieüberwachung neuer Behandlungsverfahren, wie Gentherapie und Immunotargeting. Repetitive Aspirationen können über den Therapieerfolg bei minimaler Resterkrankung Auskunft geben (Zytoreduktion), immunzytochemische Untersuchung an Einzelzellen können bei der Erforschung der Pathogenese der Metastasierung, insbesondere in den Knochen, hilfreich sein. Die Phänotypisierung der Zellen könnte Aussagen zur metastatischen Potenz und zur Frage der “cell dormancy” erlauben.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: tumour cell detection ; cathepsin D ; breast cancer ; micrometastasis ; prognostic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with an elevated level of cathepsin D in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of cathepsin D detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both anterior iliac crests in 290 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: BM2, which detects tumour-associated glycoprotein TAG 12, which is typically expressed by almost all breast cancer cells, and the anti-cathepsin D antibody. 67 of 149 BM2-positive women (45%) developed metastatic disease (median follow-up time: 69 months). Of these, 15 were cathepsin D-positive (22%). Patients with cathepsin D-positive cells in bone marrow (n = 26; 9%) had a significantly shorter metastasis-free interval (38 months) compared with women who were cathepsin D-negative (64.5 months). The worst prognosis was seen in patients positive for both markers (30.5 months), followed by those who were cathepsin D-negative and BM2-positive (48 months). The detection of cathepsin D on disseminated tumour cells characterises a subgroup of patients with a poorer prognosis who should undergo more aggressive adjuvant systemic therapy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7217
    Keywords: bone metastases ; breast cancer ; clinical course ; localization of metastases ; prognosis ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although metastasis is a frequent event in breast cancer patients, insight into the clinical course, prognosis and therapy with respect to the site of the first metastases has been poor and contradictory in former investigations. Follow-up data from 648 patients with metastatic breast cancer were statistically analyzed. Patients with bone metastases at first relapse had better overall survival (median 71 vs. 48 months; p〈0.001) and survival after first metastases (median 24 vs 12 months; p〈0.001) than patients with visceral metastases at first relapse. Bone was the site of first metastasis in 46%, and 71% of patients with metastatic breast cancer developed bone metastases. The localization of the second metastatic site was of prognostic relevance in patients with first visceral metastases, but not in patients with first bone metastases. The presence of osseous metastases correlated significantly with estrogen and progesterone receptor positivity, tumor grading I/II and S-phase fraction 〈5%. The better prognosis of patients with bone metastases is not determined exclusively by hormone receptor status. The disease is significantly more stable in patients with first bone metastases than in those with first visceral metastases.
    Type of Medium: Electronic Resource
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