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Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma.

Andolfo I, Petrosino G, Vecchione L, De Antonellis P, Capasso M, Montanaro D, Gemei M, Troncone G, Iolascon A, Orditura M, Ciardiello F, De Vita F, Zollo M - BMC Cancer (2011)

Bottom Line: Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor.The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%).These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels.

View Article: PubMed Central - HTML - PubMed

Affiliation: CEINGE, Centro di Ingegneria Genetica e Biotecnologia Avanzate, Naples, Italy.

ABSTRACT

Background: Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression.

Methods: Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays.

Results: The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels.

Conclusion: The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer.

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ErbB2 copy number variations in plasma from patients with esophageal carcinoma according to VEGF plasma levels. (A) Histogram showing lack of significant correlation between erbB2 CN variations and VEGF plasma levels in all patients with EC (n. 41), as indicated. The numbers in the bars show the EC patients in each sub-group. (B, C). Kaplan-Meier survival curves for all patients with EC according to low and high plasma levels of VEGF (B), and for patients with EC and low plasma levels of VEGF according to erbB2 CN ≤2 (solid blu line) and erbB2 CN >2 (dashed green line). Data are representative of three independent experiments.
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Figure 3: ErbB2 copy number variations in plasma from patients with esophageal carcinoma according to VEGF plasma levels. (A) Histogram showing lack of significant correlation between erbB2 CN variations and VEGF plasma levels in all patients with EC (n. 41), as indicated. The numbers in the bars show the EC patients in each sub-group. (B, C). Kaplan-Meier survival curves for all patients with EC according to low and high plasma levels of VEGF (B), and for patients with EC and low plasma levels of VEGF according to erbB2 CN ≤2 (solid blu line) and erbB2 CN >2 (dashed green line). Data are representative of three independent experiments.

Mentions: We then tested erbB2 CN for possible associations with VEGF protein levels in the plasma from the same EC patients (Figure 3). The VEGF levels data were available in our tissue/serum databank collection, and have been previously published [36]. The erbB2 CN variations did not show any significant direct associations with VEGF levels in the plasma (Figure 4A). However, when the EC patients were stratified into the low and high VEGF groups, as shown in Figure 4B, high VEGF levels in the plasma of those EC patients were significantly negatively correlated to their survival rates (P < 0.00001). In a further Kaplan-Meier analysis, we also looked at the influence of erbB2 CN variations in these EC patients with low and high VEGF levels: an erbB2 CN >2 was significantly negatively correlated to the survival rate of the EC patients with low VEGF expression (P = 0.05; Figure 3C). Altogether, these results show that erbB2 CN >2 status and low VEGF levels in the plasma of these EC patients appear to be useful to stratify a subgroup of patients with worse survival rates.


Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma.

Andolfo I, Petrosino G, Vecchione L, De Antonellis P, Capasso M, Montanaro D, Gemei M, Troncone G, Iolascon A, Orditura M, Ciardiello F, De Vita F, Zollo M - BMC Cancer (2011)

ErbB2 copy number variations in plasma from patients with esophageal carcinoma according to VEGF plasma levels. (A) Histogram showing lack of significant correlation between erbB2 CN variations and VEGF plasma levels in all patients with EC (n. 41), as indicated. The numbers in the bars show the EC patients in each sub-group. (B, C). Kaplan-Meier survival curves for all patients with EC according to low and high plasma levels of VEGF (B), and for patients with EC and low plasma levels of VEGF according to erbB2 CN ≤2 (solid blu line) and erbB2 CN >2 (dashed green line). Data are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094322&req=5

Figure 3: ErbB2 copy number variations in plasma from patients with esophageal carcinoma according to VEGF plasma levels. (A) Histogram showing lack of significant correlation between erbB2 CN variations and VEGF plasma levels in all patients with EC (n. 41), as indicated. The numbers in the bars show the EC patients in each sub-group. (B, C). Kaplan-Meier survival curves for all patients with EC according to low and high plasma levels of VEGF (B), and for patients with EC and low plasma levels of VEGF according to erbB2 CN ≤2 (solid blu line) and erbB2 CN >2 (dashed green line). Data are representative of three independent experiments.
Mentions: We then tested erbB2 CN for possible associations with VEGF protein levels in the plasma from the same EC patients (Figure 3). The VEGF levels data were available in our tissue/serum databank collection, and have been previously published [36]. The erbB2 CN variations did not show any significant direct associations with VEGF levels in the plasma (Figure 4A). However, when the EC patients were stratified into the low and high VEGF groups, as shown in Figure 4B, high VEGF levels in the plasma of those EC patients were significantly negatively correlated to their survival rates (P < 0.00001). In a further Kaplan-Meier analysis, we also looked at the influence of erbB2 CN variations in these EC patients with low and high VEGF levels: an erbB2 CN >2 was significantly negatively correlated to the survival rate of the EC patients with low VEGF expression (P = 0.05; Figure 3C). Altogether, these results show that erbB2 CN >2 status and low VEGF levels in the plasma of these EC patients appear to be useful to stratify a subgroup of patients with worse survival rates.

Bottom Line: Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor.The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%).These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels.

View Article: PubMed Central - HTML - PubMed

Affiliation: CEINGE, Centro di Ingegneria Genetica e Biotecnologia Avanzate, Naples, Italy.

ABSTRACT

Background: Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression.

Methods: Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays.

Results: The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels.

Conclusion: The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer.

Show MeSH
Related in: MedlinePlus