Her2 expression on disseminated tumor cells from bone marrow of breast cancer patients.
BACKGROUND
The presence of cytokeratin (CK)-positive cells in the bone marrow (BM) of breast cancer patients is an independent prognostic marker for long-term survival. While the exact nature of these cells remains under investigation, their persistence after chemotherapy is linked to decreased survival, making them a potential therapeutic target. Targeted therapy using the her2 antibody has been shown to improve survival in breast cancer patients. We studied the her2 expression in the BM of 105 patients with CK-positive cells present and compared it with results from the primary tumor.


METHODS
BM cytospins were stained to detect CK-positive cells. In 105 patients with detectable CK-positive cells, additional staining with her2 antibody was performed. Using an automated imaging system, the her2 slides were evaluated based on the criteria of the International Society for Cellular Therapy. RESULTS were correlated with the her2 status of the primary tumor. Furthermore, the presence of her2 mRNA was examined in a subset of 27 patients using RT-PCR.


RESULTS
On 22/105 (21%) cytospins with CK-positive cells, her2-positive cells could be detected. The positivity rate for RT-PCR was 15%. Her2 overexpression on the primary tumor was 26/105 (25%). Correlation with the BM status was as follows: Hercep score 0 to 1+: 79 patients, 10 with positive BM for her2 (12%). Hercep scores 2+ to 3+: 26 patients, 12 with her2-positive bone marrows (46%) (p=0.001).


CONCLUSIONS
Her2-positive cells were detected in the BM of 15-21% of patients who were also CK-positive using immunocytochemistry and RT-PCR. Correlation exists between the presence of her2 on the primary tumor, the hercep score and the presence of her2- positive cells in the BM both with RT-PCR and immunocytochemistry. Despite this correlation, in 12.6% of patients with a her2-negative primary tumor, her2-positive cells could be detected in the BM.
Becker
Sven
S
Tübingen University Hospital, Department of Gynecology and Obstetrics, Germany. sven.becker@med.uni-tuebingen.de
Becker-Pergola
Graziella
G
Fehm
Tanja
T
Wallwiener
Diethelm
D
Solomayer
Erich-Franz
EF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007633:Keratins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases