A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells

Elizabeth M. Matthew, Lanlan Zhou, Zhaohai Yang, David T. Dicker, Sheldon Holder, Bora Lim, Ramdane Harouaka, Siyang Zheng, Joseph Drabick, Nicholas E. Lamparella, Cristina Truica, Wafik S. El-Deiry

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3662-3676
Number of pages15
JournalOncotarget
Volume7
Issue number4
DOIs
StatePublished - Jan 1 2016

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Circulating Neoplastic Cells
Carcinoma
Antibodies
Fluorescent Antibody Technique
Prostatic Neoplasms
Keratin-20
Breast Neoplasms
Keratin-7
Cultured Tumor Cells
Immunophenotyping
Hematologic Tests
Routine Diagnostic Tests
Estrogen Receptors
Colorectal Neoplasms
Lung Neoplasms
Technology
Biopsy
Antigens
Cell Line
Population

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Matthew, Elizabeth M. ; Zhou, Lanlan ; Yang, Zhaohai ; Dicker, David T. ; Holder, Sheldon ; Lim, Bora ; Harouaka, Ramdane ; Zheng, Siyang ; Drabick, Joseph ; Lamparella, Nicholas E. ; Truica, Cristina ; El-Deiry, Wafik S. / A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells. In: Oncotarget. 2016 ; Vol. 7, No. 4. pp. 3662-3676.
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Matthew, EM, Zhou, L, Yang, Z, Dicker, DT, Holder, S, Lim, B, Harouaka, R, Zheng, S, Drabick, J, Lamparella, NE, Truica, C & El-Deiry, WS 2016, 'A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells', Oncotarget, vol. 7, no. 4, pp. 3662-3676. https://doi.org/10.18632/oncotarget.6657

A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells. / Matthew, Elizabeth M.; Zhou, Lanlan; Yang, Zhaohai; Dicker, David T.; Holder, Sheldon; Lim, Bora; Harouaka, Ramdane; Zheng, Siyang; Drabick, Joseph; Lamparella, Nicholas E.; Truica, Cristina; El-Deiry, Wafik S.

In: Oncotarget, Vol. 7, No. 4, 01.01.2016, p. 3662-3676.

Research output: Contribution to journalArticle

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