Mikrometastatische Zellen im Knochenmark von Patientinnen mit Mammakarzinom

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.

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.