Autologous Bone Marrow Transplantation - Blog Science Connections

500 Occult Breast Cancer Cells in Marrow
and cytospin preparations obtained for staining with hematoxylin and eosin
and monoclonal antibodies. These techniques confirmed the presence of
tumor cells in three of the four samples and indicated that the fourth,
although yielding unusual cells in the CFCI-GEMM assay, did not appear to
contain tumor cells.
This result indicates that at least 33% (3/9) of the histologically normal
marrows harvested from patients with breast cancer contained occult tumor
cells. These tumor cells were not evident in cytospin preparations of the
material scraped from the screens and used to initiate the cultures, indicating
that the culture time may have been important for amplifying the frequency of
tumor cells in the samples. We did not routinely assay all the samples at
earlier time points, thus our results may not give a true indication of the
average time needed to detect tumor cells.
The last marrow harvest in the series ( # 142, Table 1) grew abnormal
cells in the primary cultures. A routine cytospin preparation revealed two
EMA-positive cells. This preparation contained large numbers of histiocytes
that showed a slight diffuse cytoplasmic reaction, but none were clearly
positive. In contrast, the two EMA-positive cells were clearly positive and
possessed morphological features consistent with adenocarcinoma.
DISCUSSION
These findings demonstrate that culture techniques can be used to
amplify and consequently detect occult tumor cells in marrow harvests from
candidates for ABMT. Our results suggest that at least 33% of the marrows
harvested from breast cancer patients that have been judged free of tumor
cells by conventional histologic analysis nevertheless contain occult tumor
cells. Although this estimate is preliminary because of the small sample size,
our observation emphasizes that in a significant proportion of patients, breast
cancer is a systemic rather than a regional disease and must be treated as
such.
Our culture techniques often require a period of several weeks to detect
occult tumor cells, which would not be a disadvantage for patients who are
referred early in the course of their disease or in clinical remission. Their
harvested marrow is frozen and stored for weeks to months prior to beginning
therapy, allowing adequate time for evaluation in culture.
Several factors may have contributed to the success of our long-term
culture system in detecting occult tumor cells in bone marrow. The initial
material used to establish the cultures is obtained from the screens used to
filter the entire marrow harvest. Thus, very small aggregates of metastatic
tumor cells, which would be sampled infrequently and by chance using
conventional histologic methods, may be detected by our technique.
Adequate sampling is not the only advantage gained in our culture system,
however, since examination of cytospin preparations of the harvest material