A Pilot Study to Explore Circulating Tumour Cells in Pancreatic Cancer As a Novel Biomarker

Overview

Journal Br J Cancer

Specialty Oncology

Date 2011 Dec 22

PMID 22187035

Citations 142

Authors

L Khoja

A Backen

R Sloane

L Menasce

D Ryder

M Krebs

R Board

G Clack

A Hughes

F Blackhall

J W Valle

C Dive

Affiliations

Soon will be listed here.

Abstract

Background: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study.

Patients And Methods: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms.

Results: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0-240) vs 0 (range 0-144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms.

Conclusion: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.

Citing Articles

Circulating Neoplastic-Immune Hybrid Cells Are Biomarkers of Occult Metastasis and Treatment Response in Pancreatic Cancer.

Patel R, Parappilly M, Farley H, Latour E, Wang L, Nair A Cancers (Basel). 2024; 16(21).

PMID: 39518088 PMC: 11545756. DOI: 10.3390/cancers16213650.

[The concept of the liquid biopsy in the treatment of malignant eye tumours].

Coupland S, Sonntag S, Heimann H, Grisanti S Ophthalmologie. 2024; 121(12):946-953.

PMID: 39516408 DOI: 10.1007/s00347-024-02132-3.

Multibiomarker panels in liquid biopsy for early detection of pancreatic cancer - a comprehensive review.

Reese K, Pantel K, Smit D J Exp Clin Cancer Res. 2024; 43(1):250.

PMID: 39218911 PMC: 11367781. DOI: 10.1186/s13046-024-03166-w.

Liquid Biopsy for Detection of Pancreaticobiliary Cancers by Functional Enrichment and Immunofluorescent Profiling of Circulating Tumor Cells and Their Clusters.

Gaya A, Rohatgi N, Limaye S, Shreenivas A, Ajami R, Akolkar D Cancers (Basel). 2024; 16(7).

PMID: 38611078 PMC: 11010988. DOI: 10.3390/cancers16071400.

Shishido S, Lin E, Nissen N, Courcoubetis G, Suresh D, Mason J NPJ Precis Oncol. 2024; 8(1):36.

PMID: 38360856 PMC: 10869814. DOI: 10.1038/s41698-024-00521-0.

References

Kindler H, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H . Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol. 2010; 28(22):3617-22. PMC: 2917317. DOI: 10.1200/JCO.2010.28.1386. View

Hofman V, Ilie M, Long E, Selva E, Bonnetaud C, Molina T . Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method. Int J Cancer. 2010; 129(7):1651-60. DOI: 10.1002/ijc.25819. View

Vona G, Estepa L, Beroud C, Damotte D, Capron F, Nalpas B . Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology. 2004; 39(3):792-7. DOI: 10.1002/hep.20091. View

Wind J, Tuynman J, Tibbe A, Swennenhuis J, Richel D, van Berge Henegouwen M . Circulating tumour cells during laparoscopic and open surgery for primary colonic cancer in portal and peripheral blood. Eur J Surg Oncol. 2009; 35(9):942-50. DOI: 10.1016/j.ejso.2008.12.003. View

Munz M, Baeuerle P, Gires O . The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res. 2009; 69(14):5627-9. DOI: 10.1158/0008-5472.CAN-09-0654. View

Krebs M, Hou J, Ward T, Blackhall F, Dive C . Circulating tumour cells: their utility in cancer management and predicting outcomes. Ther Adv Med Oncol. 2011; 2(6):351-65. PMC: 3126032. DOI: 10.1177/1758834010378414. View

Coumans F, Doggen C, Attard G, de Bono J, Terstappen L . All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer. Ann Oncol. 2010; 21(9):1851-1857. DOI: 10.1093/annonc/mdq030. View

Burris 3rd H, Moore M, Andersen J, Green M, Rothenberg M, Modiano M . Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997; 15(6):2403-13. DOI: 10.1200/JCO.1997.15.6.2403. View

De Giorgi V, Pinzani P, Salvianti F, Panelos J, Paglierani M, Janowska A . Application of a filtration- and isolation-by-size technique for the detection of circulating tumor cells in cutaneous melanoma. J Invest Dermatol. 2010; 130(10):2440-7. DOI: 10.1038/jid.2010.141. View

10.

Kurihara T, Itoi T, Sofuni A, Itokawa F, Tsuchiya T, Tsuji S . Detection of circulating tumor cells in patients with pancreatic cancer: a preliminary result. J Hepatobiliary Pancreat Surg. 2008; 15(2):189-95. DOI: 10.1007/s00534-007-1250-5. View

11.

Goonetilleke K, Siriwardena A . Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2006; 33(3):266-70. DOI: 10.1016/j.ejso.2006.10.004. View

12.

Cristofanilli M, Budd G, Ellis M, Stopeck A, Matera J, Miller M . Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351(8):781-91. DOI: 10.1056/NEJMoa040766. View

13.

de Bono J, Scher H, Montgomery R, Parker C, Miller M, Tissing H . Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008; 14(19):6302-9. DOI: 10.1158/1078-0432.CCR-08-0872. View

14.

Hou J, Greystoke A, Lancashire L, Cummings J, Ward T, Board R . Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. Am J Pathol. 2009; 175(2):808-16. PMC: 2716975. DOI: 10.2353/ajpath.2009.090078. View

15.

Philip P, Benedetti J, Corless C, Wong R, OReilly E, Flynn P . Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010; 28(22):3605-10. PMC: 2917315. DOI: 10.1200/JCO.2009.25.7550. View

16.

Baeuerle P, Gires O . EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007; 96(3):417-23. PMC: 2360029. DOI: 10.1038/sj.bjc.6603494. View

17.

Jiao L, Apostolopoulos C, Jacob J, Szydlo R, Johnson N, Tsim N . Unique localization of circulating tumor cells in patients with hepatic metastases. J Clin Oncol. 2009; 27(36):6160-5. DOI: 10.1200/JCO.2009.24.5837. View

18.

Friedl P, Wolf K . Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003; 3(5):362-74. DOI: 10.1038/nrc1075. View

19.

Hou J, Krebs M, Ward T, Sloane R, Priest L, Hughes A . Circulating tumor cells as a window on metastasis biology in lung cancer. Am J Pathol. 2011; 178(3):989-96. PMC: 3069884. DOI: 10.1016/j.ajpath.2010.12.003. View

20.

Allard W, Matera J, Miller M, Repollet M, Connelly M, Rao C . Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004; 10(20):6897-904. DOI: 10.1158/1078-0432.CCR-04-0378. View