Tumor cells are dislodged into the pulmonary vein during lobectomy
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 usin...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101220 https://orcid.org/0000-0003-4555-2485 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0003-0921-3144 |
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| author | Yao, Xiaosai Williamson, Christina D'Agostino, Richard S. Fitton, Torin Smaroff, Gregory G. Wittrup, Karl Dane Williams, Robert T. Love, John C Adalsteinsson, Viktor A. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Yao, Xiaosai Williamson, Christina D'Agostino, Richard S. Fitton, Torin Smaroff, Gregory G. Wittrup, Karl Dane Williams, Robert T. Love, John C Adalsteinsson, Viktor A. |
| author_sort | Yao, Xiaosai |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:03:29Z |
| format | Article |
| id | mit-1721.1/101220 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:03:29Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1012202022-09-29T17:58:33Z Tumor cells are dislodged into the pulmonary vein during lobectomy Yao, Xiaosai Williamson, Christina D'Agostino, Richard S. Fitton, Torin Smaroff, Gregory G. Wittrup, Karl Dane Williams, Robert T. Love, John C Adalsteinsson, Viktor A. 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 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. 2016-02-19T02:33:10Z 2016-02-19T02:33:10Z 2014-07 2014-05 Article http://purl.org/eprint/type/JournalArticle 00225223 http://hdl.handle.net/1721.1/101220 Yao, Xiaosai, Christina Williamson, Viktor A. Adalsteinsson, Richard S. D’Agostino, Torin Fitton, Gregory G. Smaroff, Robert T. William, K. Dane Wittrup, and J. Christopher Love. “Tumor Cells Are Dislodged into the Pulmonary Vein During Lobectomy.” The Journal of Thoracic and Cardiovascular Surgery 148, no. 6 (December 2014): 3224–3231.e5. https://orcid.org/0000-0003-4555-2485 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0003-0921-3144 en_US http://dx.doi.org/10.1016/j.jtcvs.2014.06.074 The Journal of Thoracic and Cardiovascular Surgery Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Yao, Xiaosai Williamson, Christina D'Agostino, Richard S. Fitton, Torin Smaroff, Gregory G. Wittrup, Karl Dane Williams, Robert T. Love, John C Adalsteinsson, Viktor A. Tumor cells are dislodged into the pulmonary vein during lobectomy |
| title | Tumor cells are dislodged into the pulmonary vein during lobectomy |
| title_full | Tumor cells are dislodged into the pulmonary vein during lobectomy |
| title_fullStr | Tumor cells are dislodged into the pulmonary vein during lobectomy |
| title_full_unstemmed | Tumor cells are dislodged into the pulmonary vein during lobectomy |
| title_short | Tumor cells are dislodged into the pulmonary vein during lobectomy |
| title_sort | tumor cells are dislodged into the pulmonary vein during lobectomy |
| url | http://hdl.handle.net/1721.1/101220 https://orcid.org/0000-0003-4555-2485 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0003-0921-3144 |
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