Tumor Cells are Dislodged into the Pulmonary Vein During Lobectomy
| Autor: | J. Christopher Love, Viktor A. Adalsteinsson, K. Dane Wittrup, Christina A. Williamson, Robert T. William, Richard S. D’Agostino, Xiaosai Yao, Gregory G. Smaroff, Torin P. Fitton |
|---|---|
| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Yao, Xiaosai, Adalsteinsson, Viktor Arnarson, William, Robert T., Wittrup, Karl Dane, Love, J. Christopher |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Pathology medicine.medical_specialty Lung Neoplasms Somatic cell medicine.medical_treatment VATS lobectomy DNA Mutational Analysis Polymerase Chain Reaction Article Pulmonary vein chemistry.chemical_compound Antigen Antigens Neoplasm Predictive Value of Tests Thoracoscopy medicine Biomarkers Tumor Humans Nanotechnology Thoracotomy Genetic Testing Pneumonectomy Aged Aged 80 and over medicine.diagnostic_test business.industry Thoracic Surgery Video-Assisted Epithelial cell adhesion molecule Middle Aged Epithelial Cell Adhesion Molecule Neoplastic Cells Circulating Treatment Outcome chemistry Microscopy Fluorescence Pulmonary Veins Mutation Surgery Female business Cardiology and Cardiovascular Medicine Nested polymerase chain reaction Cell Adhesion Molecules |
| Zdroj: | PMC |
| Popis: | Objective Intraoperative tumor shedding may facilitate tumor dissemination. In earlier studies, shed tumor cells were defined primarily by cytomorphological examination, and normal epithelial cells could not always be distinguished from tumor cells. We sought to accurately identify tumor cells using single-cell sequencing and determine whether these cells were mobilized into the circulation during pulmonary lobectomy. Methods Forty-two blood samples collected from the tumor-draining pulmonary vein at the end of lobectomy procedures were analyzed. Arrays of nanowells were used to enumerate and retrieve single EpCAM[superscript +] cells. Targeted sequencing of 10 to 15 cells and nested polymerase chain reaction of single cells detected somatic mutations in shed epithelial cells consistent with patient-matched tumor but not normal tissue. Results The mean number of EpCAM[superscript +] cells in video-assisted thoracoscopy (VATS) lobectomy (no wedge) specimens (n = 16) was 165 (median, 115; range, 0-509) but sampling cells from 3 patients indicated that only 0% to 38% of the EpCAM[superscript +] cells were tumor cells. The mean number of EpCAM[superscript +] cells in VATS lobectomy (wedge) specimens (n = 12) was 1128 (median, 197; range, 47-9406) and all of the EpCAM[superscript +] cells were normal epithelial cells in 2 patients sampled. The mean number of EpCAM[superscript +] cells in thoracotomy specimens (n = 14) was 238 (median, 22; range, 9-2920) and 0% to 50% of total EpCAM[superscript +] cells were tumor cells based on 4 patients sampled. Conclusions Surgery mobilizes tumor cells into the pulmonary vein, along with many normal epithelial cells. EpCAM alone cannot differentiate between normal and tumor cells. On the other hand, single-cell genetic approaches with patient-matched normal and tumor tissues can accurately quantify the number of shed tumor cells. National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) Singapore. Agency for Science, Technology and Research National Science Foundation (U.S.). Graduate Research Fellowship Janssen Pharmaceutical Ltd. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|