E. Merkle et al., IMMUNOCYTOCHEMICAL DETECTION OF TUMOR-CEL LS IN BONE-MARROW AS A PROGNOSTIC FACTOR IN BREAST-CARCINOMA, Geburtshilfe und Frauenheilkunde, 54(12), 1994, pp. 662-669
In a prospective study at the University of Erlangen, Dept. Gynaecol.
and Obstet., 228 patients with breast cancer during their primary surg
ery and 20 patients during their metastatic surgery, underwent bone ma
rrow punctions at six punction sides, which were twice at the sternum
and twice at both iliac crest. The control group was 20 patients witho
ut an invasive carcinoma. Aim of the study was to detect or exclude tu
mour cells in the bone marrow via examination of the biopsies with mon
oclonal antibodies EMA and cytokeratin and consequently to find out th
e meaning of the results as prognostic criteria by statistical measure
ments. Tumour cells in the bone marrow were detected in 46.5% (106/228
) of the patients, who underwent a bone marrow biopsy during primary s
urgery. 21% (23/106) of the patients who were bone marrow positive, bu
t only 5.75% (7/122) of the patients, who were bone marrow negative, d
eveloped metastases during a median follow-up of 20 months. This diffe
rence is statistically significant. 17 of the 30 patients with recurre
nces developed bone metastases; 16 of them were EMA-positive. The medi
an recurrence-free interval was 5 months in the bone marrow positive g
roup and therefore noticeably shorter, than in the bone marrow negativ
e patient group with 11 months. Of the nodal negative patients, 2 bone
marrow positive patients developed distant metastases. With the knowl
edge of the nodal status and bone marrow biopsy result, it was possibl
e to predict 28 of the 30 patients correctly in respect of their risk
to metastasize. The result of the bone marrow puncture was proved in a
multivariate analysis to be an independent prognostic factor. A secon
d group of patients, in which bone marrow punkture was performed durin
g surgery for recurrences, we found in 15 patients a positive tumour c
ell result in the bone marrow and all patients with additional distant
metastases were positive with regard to their bone marrow biopsy. To
prove the specificity of the method, bone marrow, samples on 20 patien
ts without an invasive carcinoma were examined. In this group, no tumo
ur cells were found in the bone marrow. The analysis showed, that the
bone marrow sampled during primary surgery of a breast carcinoma and s
tained with a monoclonal antibody EMA in combination with cytokeratin
is an independent prognostic factor. Patients with tumour cell detecti
on in their bone marrow developed recurrences earlier and more frequen
tly than bone marrow negative patients (p < 0.001).