TY - JOUR
T1 - A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells
AU - Matthew, Elizabeth M.
AU - Zhou, Lanlan
AU - Yang, Zhaohai
AU - Dicker, David T.
AU - Holder, Sheldon L.
AU - Lim, Bora
AU - Harouaka, Ramdane
AU - Zheng, Si Yang
AU - Drabick, Joseph J.
AU - Lamparella, Nicholas E.
AU - Truica, Cristina I.
AU - El-Deiry, Wafik S.
PY - 2016
Y1 - 2016
N2 - Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostatespecific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing.
AB - Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostatespecific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing.
UR - https://www.scopus.com/pages/publications/84957990887
UR - https://www.scopus.com/pages/publications/84957990887#tab=citedBy
U2 - 10.18632/oncotarget.6657
DO - 10.18632/oncotarget.6657
M3 - Article
C2 - 26695546
AN - SCOPUS:84957990887
SN - 1949-2553
VL - 7
SP - 3662
EP - 3676
JO - Oncotarget
JF - Oncotarget
IS - 4
ER -