TY - JOUR
T1 - Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel
AU - Mitas, Michael
AU - Mikhitarian, Kaidi
AU - Walters, Kenneth C
AU - Baron, Paul L.
AU - Elliott, Bruce M.
AU - Brothers, Thomas E.
AU - Robison, Jay G.
AU - Metcalf, John S.
AU - Palesch, Yuko Y.
AU - Zhang, Zhen
AU - Gillanders, William E.
AU - Cole, David J.
PY - 2001/7/15
Y1 - 2001/7/15
N2 - Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 × 105-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 × 106-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mare, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.
AB - Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 × 105-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 × 106-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mare, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.
KW - Axillary lymph node
KW - Breast cancer genes
KW - Diagnostic
KW - ROC analysis
KW - SYBR Green I chemistry
KW - Sentinel lymph node
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U2 - 10.1002/ijc.1312
DO - 10.1002/ijc.1312
M3 - Article
C2 - 11410861
AN - SCOPUS:0035879753
SN - 0020-7136
VL - 93
SP - 162
EP - 171
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -
