Disseminated Single Tumor Cells as Detected by Real-Time Quantitative Polymerase Chain Reaction Represent a Prognostic Factor in Patients Undergoing Surgery for Colorectal Cancer

Güller, Ulrich; Zajac, Paul; Schnider, Annelies; Bösch, Beatrix; Vorburger, Stefan; Zuber, Markus; Spagnoli, Giulio C.; Oertli, Daniel; Maurer, Robert; Metzger, U; Harder, F; Heberer, Michael; Marti, Walter R.

doi:10.1097/00000658-200212000-00009

Cited by 145 publications

(109 citation statements)

References 40 publications

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“…Eight studies were excluded as they reported only on preoperative blood sampling (Bessa et al, 2001;Fujita et al, 2001;Wong et al, 2001;Zhang et al, 2005;Douard et al, 2006;Iinuma et al, 2006;Wang et al, 2006;Friederichs et al, 2007). Nine studies were excluded as they contained data from which outcomes could not be extracted, of which four were excluded as they combined positive results of molecular detection of multiple samples and their effect on prognosis (Hardingham et al, 2000;Guller et al, 2002;Bosch et al, 2003;Koyanagi et al, 2008), and five were excluded as it was impossible to extract the data for outcomes of interest (White and Griffiths, 1976;Funaki et al, 1998;Wyld et al, 1998;Conzelmann et al, 2005;Wang et al, 2007). Five studies were excluded as they were reviews or systematic reviews, which did not report on prognostic outcomes (Tsavellas et al, 2001;Sleijfer et al, 2007;Riethdorf et al, 2008;Sergeant et al, 2008;Tsouma et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

et al. 2010

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Background: The role of adjuvant chemotherapy after resection of colorectal cancers (CRCs) is well understood for patients with stage-I or stage-III disease. Its efficacy for those with stage-II disease remains much less clear. Many investigators have sought to identify prognostic markers that might clarify which patients have the highest risk of recurrence and would, therefore, be most likely to benefit from chemotherapy. This systematic review examines evidence for the use of peripherally sampled, circulating tumour cells (CTCs) as such a prognostic marker. Methods: A comprehensive literature search was used to identify studies reporting on the significance of CTCs in the postoperative blood of CRC patients. Results: Fourteen studies satisfied the inclusion criteria. Six of the nine studies that took blood samples 24 h or more postoperatively found detection of postoperative CTCs to be an independent predictor of cancer recurrence. Conclusion: The presence of CTCs in peripheral blood at least 24 h after resection of CRCs is an independent prognostic marker of recurrence. Further studies are needed to clarify the optimal time point for blood sampling and determine the benefit of chemotherapy in CTC-positive patients with stage-II disease.

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Section: Resultsmentioning

confidence: 99%

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

et al. 2010

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“…Viable cancer cells can be recovered from surgical sites, the lymphatics, and venous circulation during both tumor resection and metastasis (21,22,55,62). The formation of secondary tumors requires the adhesion of these cells to surrounding tissues.…”

Section: Discussionmentioning

confidence: 99%

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Craig¹,

Gayer²,

Schaubert³

et al. 2009

American Journal of Physiology-Cell Physiology

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. Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of ␤1-integrin at threonine 788/789. Am J Physiol Cell Physiol 296: C193-C204, 2009. First published November 12, 2008 doi:10.1152/ajpcell.00355.2008.-Increased extracellular pressure stimulates ␤1-integrin-dependent cancer cell adhesion. We asked whether pressure-induced adhesion is mediated by changes in ␤1-integrin binding affinity or avidity and whether these changes are phosphorylation dependent. We evaluated integrin affinity and clustering in human SW620 colon cancer cells by measuring differences in binding between soluble Arg-Gly-Asp (RGD)-Fc ligands and RGD-Fc-F(abЈ)2 multimeric complexes under ambient and 15-mmHg increased pressures. Phosphorylation of ␤1-integrin S785 and T788/9 residues in SW620 and primary malignant colonocytes was assessed in parallel. We further used GD25-␤1-integrin-null murine fibroblasts stably transfected with either wild-type ␤1A-integrin, S785A, TT788/9AA, or T788D mutants to investigate the role of ␤1-integrin site-specific phosphorylation. SW620 binding of RGD-Fc-F(abЈ)2 multimeric complexes, but not soluble RGD-Fc ligands, was sensitive to integrin clustering. RGD-Fc ligand binding was significantly increased under elevated pressure, suggesting that pressure modulates ␤1-integrin affinity. Pressure stimulated both ␤1-integrin S785 and T788/9 phosphorylation. GD25-␤1A-integrin wild-type and S785A cells displayed an increase in adhesion to fibronectin under elevated pressure, an effect absent in ␤1-integrin-null and TT788/9AA cells. T788D substitution significantly elevated basal cell adhesion but displayed no further increase under pressure. These results suggest pressure-induced cell adhesion is mediated by ␤1-integrin T788/9 phosphorylation-dependent changes in integrin binding affinity. adhesion; mechanotransduction; metastasis INTEGRIN-MEDIATED TUMOR CELL adhesion to extracellular matrix components or endothelial cells is an important step in the development of metastatic lesions. Integrin binding affinity is regulated by distinct receptor activation states (23). Initial cell attachment requires integrin activation by cytoplasmic signals that convey large conformational changes to the extracellular domain and enhance ligand-binding affinity (56). The avidity and strength of the interaction is further increased through the redistribution of integrins in the cell membrane, often referred to as receptor clustering (65). The tendency of some malignancies to exhibit reduced integrin expression while maintaining adhesive properties underscores the significance of integrin activation states in mediating tumor cell adhesion (33, 47).Likewise, mutations conferring constitutive integrin activation have been shown to directly contribute to the metastatic potential of cancer cells (20,53). Mechanisms underlying integrin affinity and avidity modulation are therefore of significant interest in the control of tumor metastasis.It is increasingly clear that integrin modulation may...

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“…In contrast, CEA has been reported to be a reliable target for the detection of disseminated gastric cancer cells, and is the most common marker for detecting micrometastasis with RT -PCR (Kodera et al, 1998;Nakanishi et al, 2000;Osaka et al, 2004). The quantitative RT -PCR method using multiple markers reportedly improved the sensitivity and specificity of the quantitative RT -PCR method (Guller et al, 2002;Timar et al, 2002;Osaka et al, 2004;Fujita et al, 2006). We therefore selected the combination of CEA and CK-20 as diagnostic markers for predicting micrometastasis in patients with gastric carcinoma in this study.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

et al. 2007

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Identification of cancer cells in the peritoneal cavity could influence therapy and outcome of gastric carcinoma patients. The objective of this study was to evaluate the clinical impact of the real-time quantitative polymerase chain reaction-(PCR) based identification of isolated tumour cells in the peritoneal lavage fluid of gastric carcinoma. The peritoneal lavage fluid of 116 patients with gastric cancer was sampled at laparotomy. After RNA extraction and reverse transcription, real-time quantitative PCR was performed using the primers and probes for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK20). When either the CEA mRNA or CK20 mRNA level of the sample was over the cutoff value, the sample was determined to be PCR-positive. Forty-six (40%) of the 116 patients were PCR-positive and 30 (65%) of the 46 PCR-positive patients died as a result of recurrent peritoneal dissemination. The prognosis of the 46 PCR-positive patients was significantly (Po0.001) worse than that of 70 PCR-negative patients. Furthermore, in 80 of the cases with a curative R0 resection, 15 of the patients with PCR-positive findings had a significantly (Po0.001) poorer prognosis than the 65 PCR-negative patients. The prognosis of the PCR-positive patients was significantly poorer than that of the PCR-negative patients in the T3 (Po0.0001) and T4 (P ¼ 0.048) subgroups. In a multivariate analysis of the 80 cases with a curative R0 resection, the real-time quantitative RT -PCR (CEA and/or CK20) levels indicated that they were independent prognostic factors. The real-time quantitative RT -PCR analysis of the CEA and/or CK20 transcripts in the peritoneal lavage fluid is useful for predicting the peritoneal recurrence in patients who are undergoing a curative resection for gastric cancer.

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Disseminated Single Tumor Cells as Detected by Real-Time Quantitative Polymerase Chain Reaction Represent a Prognostic Factor in Patients Undergoing Surgery for Colorectal Cancer

Cited by 145 publications

References 40 publications

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

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Disseminated Single Tumor Cells as Detected by Real-Time Quantitative Polymerase Chain Reaction Represent a Prognostic Factor in Patients Undergoing Surgery for Colorectal Cancer

Cited by 145 publications

References 40 publications

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β1-integrin at threonine 788/789

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

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Increased extracellular pressure enhances cancer cell integrin-binding affinity through phosphorylation of β₁-integrin at threonine 788/789