A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker

Khoja, Leila; Backen, Alison; Szczepaniak-Sloane, Robert; Menasce, Lia P; Ryder, W. David J.; Krebs, Matthew; Board, Ruth; Clack, Glen; Hughes, Andrew; Blackhall, Fiona; Valle, Juan W; Dive, Caroline

doi:10.1038/bjc.2011.545

Cited by 228 publications

(232 citation statements)

References 42 publications

(59 reference statements)

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“…We used procedures of this platform and CTCs definition criteria according to previous detailed reports. 33 ISET membrane spots were cut and submitted to immunocytochemistry with anti-CD45 antibody (1:100; clone 2B11 C PD7/26, Dako TM ), a surface leukocyte marker, in order to differentiate them from the CTCs. For CTCs counting, 8 spots from the ISET filter were used (corresponding to 8 mL of blood), after staining with hematoxylin and eosin.…”

Section: Patientsmentioning

confidence: 99%

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Buim

Fanelli

Souza

et al. 2015

Cancer Biology & Therapy

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Background: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. Objective: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. Methods: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). Results: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P D 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. Conclusion: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.

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Section: Patientsmentioning

confidence: 99%

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Buim

Fanelli

Souza

et al. 2015

Cancer Biology & Therapy

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“…In one study based on the ISET method, CTCs were found in 18 of 29 patients (62.0%) with primary invasive melanoma and in five out of eight patients (62.5%) with metastatic melanoma (De Giorgi et al, 2010). Khoja et al (2012) compared CellSearch and ISET in terms of CTC detection in 54 patients with pancreatic cancer, and found that ISET detects a higher number of CTCs than the CellSearch System. Polymerase chain reaction (PCR)‐based methods are also commonly used; CTCs were detected in 33.8–84% of patients by using Nested PCR with CK20 mRNA as a CTC marker in different studies (Soeth et al, 2005; Zhou et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

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Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4′,6‐diamidino‐2‐phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45‐/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2–5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7–7.3, p < 0.001) were both associated with shorter disease‐free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2–6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8–8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

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“…Although the liver is the most common target of pancreatic cancer with the exception of the lymph nodes, effective methods for prediction and treatment of liver metastasis remain unestablished (7,8). Identification of prognostic markers of metastasis would be useful for the management of post-operative patients with pancreatic cancer (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL

Chijiiwa

Moriyama

Ohuchida

et al. 2016

International Journal of Oncology

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Abstract.Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P= 0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti-metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer.

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A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker

Cited by 228 publications

References 42 publications

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL

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