Am. Vannucchi et al., Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT-PCR for cytokeratin-19 mRNA, BR J HAEM, 103(3), 1998, pp. 610-617
There is considerable interest in an autologous transplantation (AT) progra
mme for patients with high-risk breast cancer; however, the issue of the in
cidence of occult bone marrow (BM) micrometastasis at diagnosis, and the ca
ncer contamination of peripheral blood stem cell (PBSC) collections used fo
r haematological rescue, is still debated. The presence of BM micrometastas
is was evaluated in bilateral BM biopsies obtained at diagnosis of 33 patie
nts with stage II/IIIA breast cancer using: (i) a 'nested' reverse transcri
ptase-polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (K19) mRN
A, (ii) histology, and (iii) immunohistochemistry (IHC) analysis with a pan
el of three monoclonal antibodies. The RT-PCR assay only was used to determ
ine contamination of PBSC collections obtained after priming with recombina
nt human granulocyte-colony stimulating factor (rhG-CSF). K19 transcripts i
n one or both BM samples were detected in 48% of patients at diagnosis, wit
h an overall 85% concordance with the results of IHC analysis. On the other
hand, 56% of PCR- and IHC-positive BM samples were diagnosed as 'normal' o
n histological analysis. 57% of patients showed K19 mRNA in at least one PB
SC collection; the possibility to hare contaminated PBSC collections was si
gnificantly higher in patients with K19 positivity in BM at diagnosis. In f
our patients who had shown K19 positivity in BM and in PBSC collections, im
munoselected CD34(+) cells used for haematological rescue were K19-negative
. There was a trend towards longer relapse free survival (RFS) in patients
transplanted with K19-negative PBSC collections as compared to the others.
In conclusion, a substantial proportion of patients with high-risk non-meta
static breast cancer present occult BM micrometastasis at diagnosis and als
o show cancer contamination of PBSC collections used for AT. These might re
present a category of patients with poorer prognosis after AT, and possible
candidates for more intensive and/or alternative therapeutic regimens, inc
luding AT with purged PBSCs.