Lack of correlation between P53 expression, BCL-2 expression, apoptosis and ex vivo chemosensitivity in advanced human breast cancer.
The relationship between apoptosis and chemosensitivity remains complex. We tested the chemosensitivity of 45 patients with advanced breast cancer (BC) ex vivo against anthracyclines (A: doxorubicin, epirubicin), taxanes (T: paclitaxel, docetaxel), cisplatin (DDP) and CMF and any correlation with the expression of p53, Bcl-2 and apoptosis. Viable cells were processed for ex vivo ATP Tumor Chemosensitivity Assay (ATP-TCA). Immunohistochemistry was performed in corresponding tumor samples. Apoptosis prior to chemotherapy was assayed using a TUNEL Test. Of 45 BC tested, 18 (40%) were p53+ and 37 (82%) showed high Bcl-2 expression. Apoptosis was detected in 29 (64.4%) specimens. The Ex vivo Response Rate (EVRR) for T was 75.6% in all cases. This was the highest rate among the 4 drugs tested followed by CMF (66.7%). For A and DDP the positive rates were lower (27.6% and 10.6%, respectively). A significant correlation (r = 0.589, p < or = 0.01) was found between tumors which were sensitive to A and DDP. There was no association between chemosensitivity and apoptosis. Moreover tests for p53 and Bcl-2 did not show a correlation to ex vivo chemosensitivity. Pretreatment apoptotic parameters are unlikely to predict the individual response of breast cancer to antineoplastic agents.
Rein
D T
DT
Department of Gynecology and Obstetrics, University of Cologne, Kerpener Strasse 34, D-50931 Cologne, Germany.
Schöndorf
T
T
Breidenbach
M
M
Janát
M M
MM
Weikelt
A
A
Göhring
U J
UJ
Becker
M
M
Mallmann
P
P
Kurbacher
C M
CM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013223:Statistics as Topic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53