Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients

Albuquerque, Andreia; Kubisch, Ilja; Stölzel, Ulrich; Ernst, Dominikus; Boese-Landgraf, J.; Breier, Georg; Stamminger, Gudrun; Fersis, N.; Kaul, S.

doi:10.1186/1479-5876-10-222

Cited by 56 publications

(52 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 Another study provided evidence of a strong correlation between CTC detection and radiographic disease progression in patients receiving chemotherapy for CRC. 15 In agreement with these findings, a recent meta-analysis demonstrated that the detection of CTCs in patients with resectable CRC liver metastases is associated with poor survival. 23 Finally, serum CEA levels did not correlate with high tumor burden in the liver, however the statistical power to verify this relationship may not have enough strength.…”

Section: Discussionmentioning

confidence: 56%

“…[12][13][14] In addition, a strong correlation between detection of CTCs and radiographic disease progression in patients receiving chemotherapy for CRC has been demonstrated. 15 We hypothesized that the quantity of baseline CTCs is associated with the tumor burden in the liver in patients with a novel stage IV CRC diagnosis. The study demonstrates that CTC quantity correlates with high tumor burden in the liver and elevated serum CEA levels in stage IV CRC patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

Kaifi¹,

Kunkel

Dicker

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

Background: Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Methods: Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAMC CTCs were analyzed with the FDA-approved CellSearch Ò system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. Results: CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch Ò detection was 6.3 (SEM 2.9). High baseline CTC numbers (3) correlated significantly with a high tumor/liver ratio (30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. Conclusions: High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

Kaifi¹,

Kunkel

Dicker

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…9 Several studies have shown that CTC detection is an important prognostic factor in patients with mCRC. [10][11][12][13][14] High levels of CTCs are correlated with worse prognosis in breast cancer and their decrease after treatment are related to better survival. 15 More recently, liquid biopsy technology, such as CTCs, have shown to be able to provide real time information about the tumor biology.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…We previously conducted studies demonstrating that immunomagnetic enrichment followed by real-time PCR analysis of the tumor-associated genes keratin 19 (KRT19) , mucin 1 (MUC1) , epithelial cell adhesion molecule (EPCAM) , carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and survivin (BIRC5) can be used to detect CTC as independent predictors of progression-free survival (PFS) in patients with pancreatic [10] and colon cancer [11]. …”

Section: Introductionmentioning

confidence: 99%

Prognostic Role of a Multimarker Analysis of Circulating Tumor Cells in Advanced Gastric and Gastroesophageal Adenocarcinomas

et al. 2015

Self Cite

View full text Add to dashboard Cite

Objective: We aimed to assess the prognostic value of circulating tumor cells (CTC) in patients with advanced gastric and gastroesophageal adenocarcinomas. Methods: The presence of CTC was evaluated in 62 patients with advanced gastric and gastroesophageal adenocarcinomas before systemic therapy and at follow-up through immunomagnetic enrichment for mucin 1- and epithelial cell adhesion molecule (EpCAM)-positive cells, followed by real-time RT-PCR of the tumor-associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. Results: The patients were stratified into groups according to CTC detection (CTC negative: with all marker genes negative; CTC positive: with at least 1 of the marker genes positive). Patients who were CTC positive at baseline had a significantly shorter median progression-free survival (PFS; 3.5 months, 95% CI: 2.9-4.2) and overall survival (OS; 5.8 months, 95% CI: 4.5-7.0) than patients lacking CTC (PFS 10.7 months, 95% CI: 6.9-14.4, p < 0.001; OS 13.3 months, 95% CI: 8.0-18.6, p = 0.003). Alterations in the marker profile during the course of chemotherapy were not predictive of clinical outcome or response to therapy. Yet, a favorable clinical response depended significantly on CTC negativity (p = 0.03). Conclusion: Our data suggest that the presence of CTC is a major predictor of outcome in patients with gastric and gastroesophageal malignancies.

show abstract

Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients

Cited by 56 publications

References 13 publications

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

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

Prognostic Role of a Multimarker Analysis of Circulating Tumor Cells in Advanced Gastric and Gastroesophageal Adenocarcinomas

Contact Info

Product

Resources

About