title: Lack of correlation between P53 expression, BCL-2 expression, apoptosis and ex vivo chemosensitivity in advanced human breast cancer.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, University of Cologne, Kerpener Strasse 34, D-50931 Cologne, Germany.
authors.forename: D T
authors.initials: DT
authors.lastname: Rein
authors.forename: T
authors.initials: T
authors.lastname: Schöndorf
authors.forename: M
authors.initials: M
authors.lastname: Breidenbach
authors.forename: M M
authors.initials: MM
authors.lastname: Janát
authors.forename: A
authors.initials: A
authors.lastname: Weikelt
authors.forename: U J
authors.initials: UJ
authors.lastname: Göhring
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: P
authors.initials: P
authors.lastname: Mallmann
authors.forename: C M
authors.initials: CM
authors.lastname: Kurbacher
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53