Systematic analysis of in vitro chemosensitivity and mib-1 expression in molecular breast cancer subtypes.
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Systematic analysis of in vitro chemosensitivity and mib-1 expression in molecular breast cancer subtypes. / Liedtke, Cornelia; Packeisen, Jens; Hess, Kenneth R; Vogt, Ulf; Kiesel, Ludwig; Kersting, Christian; Korsching, Eberhardt; Brandt, Burkhard; Buerger, Horst.
In: EUR J CANCER, Vol. 48(13), 2012, p. 2066-2074.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Systematic analysis of in vitro chemosensitivity and mib-1 expression in molecular breast cancer subtypes.
AU - Liedtke, Cornelia
AU - Packeisen, Jens
AU - Hess, Kenneth R
AU - Vogt, Ulf
AU - Kiesel, Ludwig
AU - Kersting, Christian
AU - Korsching, Eberhardt
AU - Brandt, Burkhard
AU - Buerger, Horst
PY - 2012
Y1 - 2012
N2 - BACKGROUND: Molecular breast cancer subgroups show differences with regard to prognosis and response to chemotherapy. In vitro chemotherapy sensitivity and resistance assays (CSRAs) are a means to directly evaluate tumour cell response to a given drug. METHODS: Using tissue microarray (TMA) analysis, 550 invasive breast cancers were investigated for the expression of oestrogen receptor (ER), progesterone receptor (PR), vimentin, Ck5, Ck14, Ck19, HER2 and Mib-1/Ki-67. All carcinomas were subjected to in vitro CSRA analysis using three separate chemotherapy combinations. In vitro chemotherapy sensitivity was established using an adenosine triphosphate (ATP) bioluminescence assay. Results of immunohistochemical staining and in vitro response were correlated. RESULTS: Mib-1 expression was associated with sensitivity against Paclitaxel/Epirubicin (p=0.014) and Docetaxel/Epirubicin (p=0.014). Mib-1 expression was positively/negatively correlated with expression of basal/luminal markers, respectively. Hierarchical clustering revealed three subtypes, resembling luminal, basal-like and HER2-like breast cancer subtypes. In vitro response for Paclitaxel/Epirubicin was most frequently observed for cases in the basal category (40.3%) compared to HER2-like (25.8%) and luminal cases (28.6%). In multivariate analysis expression of Mib-1 was not a significant independent predictor of in vitro response to chemotherapy. CONCLUSION: Breast cancer molecular subclasses show differences regarding in vitro chemotherapy sensitivity. These may in part explain differences observed between breast cancer molecular subtypes in vivo.
AB - BACKGROUND: Molecular breast cancer subgroups show differences with regard to prognosis and response to chemotherapy. In vitro chemotherapy sensitivity and resistance assays (CSRAs) are a means to directly evaluate tumour cell response to a given drug. METHODS: Using tissue microarray (TMA) analysis, 550 invasive breast cancers were investigated for the expression of oestrogen receptor (ER), progesterone receptor (PR), vimentin, Ck5, Ck14, Ck19, HER2 and Mib-1/Ki-67. All carcinomas were subjected to in vitro CSRA analysis using three separate chemotherapy combinations. In vitro chemotherapy sensitivity was established using an adenosine triphosphate (ATP) bioluminescence assay. Results of immunohistochemical staining and in vitro response were correlated. RESULTS: Mib-1 expression was associated with sensitivity against Paclitaxel/Epirubicin (p=0.014) and Docetaxel/Epirubicin (p=0.014). Mib-1 expression was positively/negatively correlated with expression of basal/luminal markers, respectively. Hierarchical clustering revealed three subtypes, resembling luminal, basal-like and HER2-like breast cancer subtypes. In vitro response for Paclitaxel/Epirubicin was most frequently observed for cases in the basal category (40.3%) compared to HER2-like (25.8%) and luminal cases (28.6%). In multivariate analysis expression of Mib-1 was not a significant independent predictor of in vitro response to chemotherapy. CONCLUSION: Breast cancer molecular subclasses show differences regarding in vitro chemotherapy sensitivity. These may in part explain differences observed between breast cancer molecular subtypes in vivo.
M3 - SCORING: Journal article
VL - 48(13)
SP - 2066
EP - 2074
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
ER -