Limits...
Disseminated tumour cells as a prognostic biomarker in colorectal cancer.

Flatmark K, Borgen E, Nesland JM, Rasmussen H, Johannessen HO, Bukholm I, Rosales R, Hårklau L, Jacobsen HJ, Sandstad B, Boye K, Fodstad Ø - Br. J. Cancer (2011)

Bottom Line: Associations between the presence of DTC and metastasis-free, disease-specific and overall survival were analysed using univariate and multivariate methods.The presence of DTC was associated with adverse outcome (metastasis-free, disease-specific and overall survival) in univariate and multivariate analyses.The presence of DTC was associated with adverse prognosis in this cohort of patients curatively resected for CRC, suggesting that DTC detection still holds promise as a biomarker in CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo 0424, Norway. kjersti.flatmark@rr-research.no

ABSTRACT

Background: The study was performed to determine detection rate and prognostic relevance of disseminated tumour cells (DTC) in patients receiving curatively intended surgery for colorectal cancer (CRC).

Methods: The study population consisted of 235 patients with CRC prospectively recruited from five hospitals in the Oslo region. Bone marrow (BM) aspirates were collected at the time of surgery and the presence of DTC was determined by two immunological methods; immunomagnetic selection (using an anti-EpCAM antibody) and immunocytochemistry (using a pan-cytokeratin antibody). Associations between the presence of DTC and metastasis-free, disease-specific and overall survival were analysed using univariate and multivariate methods.

Results: Disseminated tumour cells were detected in 41 (17%) and 28 (12%) of the 235 examined BM samples by immunomagnetic selection and immunocytochemistry, respectively, with only five samples being positive with both methods. The presence of DTC was associated with adverse outcome (metastasis-free, disease-specific and overall survival) in univariate and multivariate analyses.

Conclusion: The presence of DTC was associated with adverse prognosis in this cohort of patients curatively resected for CRC, suggesting that DTC detection still holds promise as a biomarker in CRC.

Show MeSH

Related in: MedlinePlus

Kaplan–Meier survival plots demonstrating the association between the presence of disseminated tumour cells in bone marrow and metastasis-free survival in stage subgroups at diagnosis. Immunomagnetic selection (IMS) in TNM stages 1 (A), 2 (B) and 3 (C). Immunocytochemistry (ICC) in TNM stages 1 (D), 2 (E) and 3 (F).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3101945&req=5

fig2: Kaplan–Meier survival plots demonstrating the association between the presence of disseminated tumour cells in bone marrow and metastasis-free survival in stage subgroups at diagnosis. Immunomagnetic selection (IMS) in TNM stages 1 (A), 2 (B) and 3 (C). Immunocytochemistry (ICC) in TNM stages 1 (D), 2 (E) and 3 (F).

Mentions: The detection of tumour cells in BM was associated with adverse prognosis in this cohort of CRC patients (Figure 1; Table 4). The presence of EpCAM-positive cells, as detected by IMS, was inversely associated with metastasis-free, disease-specific and overall survival in univariate analyses (P-values 0.049, 0.03 and 0.02, respectively). Immunocytochemistry detection of cytokeratin-positive cells was inversely associated with metastasis-free and disease-specific survival, but not with overall survival (P-values 0.03, 0.002 and 0.06, respectively). In multivariate Cox regression analyses, the impact of detecting EpCAM-positive cells in BM remained evident for metastasis-free survival (Table 4), as well as for disease-specific (P=0.002; HR=3.0; CI=1.5–5.8) and overall survival (P=0.006; HR=1.9; CI=1.2–3.0). For cytokeratin-positive cells, an association was preserved in multivariate analysis only for disease-specific survival (P=0.01; HR=2.5; CI=1.2–5.0). Additional analyses were then performed to assess whether the influence of DTC had particular relevance in classic prognostic subgroups defined by the TNM staging system. In univariate analyses, the prognostic significance of IMS-detected EpCAM-positive cells was evident in TNM stage 3, whereas significant impact of ICC-detected cytokeratin-positive cells was confined to TNM stage 2 (Figure 2).


Disseminated tumour cells as a prognostic biomarker in colorectal cancer.

Flatmark K, Borgen E, Nesland JM, Rasmussen H, Johannessen HO, Bukholm I, Rosales R, Hårklau L, Jacobsen HJ, Sandstad B, Boye K, Fodstad Ø - Br. J. Cancer (2011)

Kaplan–Meier survival plots demonstrating the association between the presence of disseminated tumour cells in bone marrow and metastasis-free survival in stage subgroups at diagnosis. Immunomagnetic selection (IMS) in TNM stages 1 (A), 2 (B) and 3 (C). Immunocytochemistry (ICC) in TNM stages 1 (D), 2 (E) and 3 (F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101945&req=5

fig2: Kaplan–Meier survival plots demonstrating the association between the presence of disseminated tumour cells in bone marrow and metastasis-free survival in stage subgroups at diagnosis. Immunomagnetic selection (IMS) in TNM stages 1 (A), 2 (B) and 3 (C). Immunocytochemistry (ICC) in TNM stages 1 (D), 2 (E) and 3 (F).
Mentions: The detection of tumour cells in BM was associated with adverse prognosis in this cohort of CRC patients (Figure 1; Table 4). The presence of EpCAM-positive cells, as detected by IMS, was inversely associated with metastasis-free, disease-specific and overall survival in univariate analyses (P-values 0.049, 0.03 and 0.02, respectively). Immunocytochemistry detection of cytokeratin-positive cells was inversely associated with metastasis-free and disease-specific survival, but not with overall survival (P-values 0.03, 0.002 and 0.06, respectively). In multivariate Cox regression analyses, the impact of detecting EpCAM-positive cells in BM remained evident for metastasis-free survival (Table 4), as well as for disease-specific (P=0.002; HR=3.0; CI=1.5–5.8) and overall survival (P=0.006; HR=1.9; CI=1.2–3.0). For cytokeratin-positive cells, an association was preserved in multivariate analysis only for disease-specific survival (P=0.01; HR=2.5; CI=1.2–5.0). Additional analyses were then performed to assess whether the influence of DTC had particular relevance in classic prognostic subgroups defined by the TNM staging system. In univariate analyses, the prognostic significance of IMS-detected EpCAM-positive cells was evident in TNM stage 3, whereas significant impact of ICC-detected cytokeratin-positive cells was confined to TNM stage 2 (Figure 2).

Bottom Line: Associations between the presence of DTC and metastasis-free, disease-specific and overall survival were analysed using univariate and multivariate methods.The presence of DTC was associated with adverse outcome (metastasis-free, disease-specific and overall survival) in univariate and multivariate analyses.The presence of DTC was associated with adverse prognosis in this cohort of patients curatively resected for CRC, suggesting that DTC detection still holds promise as a biomarker in CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo 0424, Norway. kjersti.flatmark@rr-research.no

ABSTRACT

Background: The study was performed to determine detection rate and prognostic relevance of disseminated tumour cells (DTC) in patients receiving curatively intended surgery for colorectal cancer (CRC).

Methods: The study population consisted of 235 patients with CRC prospectively recruited from five hospitals in the Oslo region. Bone marrow (BM) aspirates were collected at the time of surgery and the presence of DTC was determined by two immunological methods; immunomagnetic selection (using an anti-EpCAM antibody) and immunocytochemistry (using a pan-cytokeratin antibody). Associations between the presence of DTC and metastasis-free, disease-specific and overall survival were analysed using univariate and multivariate methods.

Results: Disseminated tumour cells were detected in 41 (17%) and 28 (12%) of the 235 examined BM samples by immunomagnetic selection and immunocytochemistry, respectively, with only five samples being positive with both methods. The presence of DTC was associated with adverse outcome (metastasis-free, disease-specific and overall survival) in univariate and multivariate analyses.

Conclusion: The presence of DTC was associated with adverse prognosis in this cohort of patients curatively resected for CRC, suggesting that DTC detection still holds promise as a biomarker in CRC.

Show MeSH
Related in: MedlinePlus