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Association of angiogenic factors with prognosis in esophageal cancer.

Dreikhausen L, Blank S, Sisic L, Heger U, Weichert W, Jäger D, Bruckner T, Giese N, Grenacher L, Falk C, Ott K, Schmidt T - BMC Cancer (2015)

Bottom Line: No significant difference was found in survival between SCC and AEG (p = 0.90). 26 patients were histopathological responders.Angiogenic factors were associated with the following clinicopathological factors: tumor tissue expression of Angiopoietin-2 and Follistatin was higher in SCC compared to AEG (p = 0.022 and p = 0.001).No association with prognosis was found in the patients' serum.

View Article: PubMed Central - PubMed

Affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. lena.dreikhausen@tesionmail.de.

ABSTRACT

Background: Despite multimodal therapy esophageal cancer often presents with poor prognosis. To improve outcome, tumor angiogenesis and anti-angiogenic therapeutic agents have recently gained importance. However, patient subgroups who benefit from anti-angiogenic therapy are not yet defined. In this retrospective exploratory study we investigated 9 angiogenic factors in patients' serum and tissue samples with regard to their association with clinicopathological parameters, prognosis and response in patients with locally advanced preoperatively treated esophageal cancer.

Methods: From 2007 to 2012 preoperative serum and corresponding tumor tissue (n = 54), only serum (n = 20) or only tumor tissue (n = 4) were collected from esophageal squamous cell carcinoma (SCC) (n = 34) and adenocarcinoma of the esophagogastric junction (AEG) (n = 44) staged cT3/4NanyM0/x after preoperative chemo(radio)therapy. Angiogenic cytokine levels in both tissue and serum were measured by multiplex immunoassay.

Results: Median survival in all patients was 28.49 months. No significant difference was found in survival between SCC and AEG (p = 0.90). 26 patients were histopathological responders. Histopathological response was associated with prognosis (p = 0.05). Angiogenic factors were associated with the following clinicopathological factors: tumor tissue expression of Angiopoietin-2 and Follistatin was higher in SCC compared to AEG (p = 0.022 and p = 0.001). High HGF and Follistatin expression in the tumor tissue was associated with poor prognosis in all patients (p = 0.037 and p = 0.036). No association with prognosis was found in the patients' serum. Neither patients' serum nor tumor tissue showed an association between angiogenic factors and response to neoadjuvant therapy.

Conclusion: Two angiogenic factors (HGF and Follistatin) in posttherapeutic tumor tissue are associated with prognosis in esophageal cancer patients. Biological differences of AEG and SCC with respect to angiogenesis were evident by the different expression of 2 angiogenic factors. Results are promising and should be pursued prospectively, optimally sequentially pre- and posttherapeutically.

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Prognostic cytokines in the tissue of esophageal cancer patients. Kaplan-Maier plots for overall survival of esophageal cancer patients according to A) tissue protein levels of HGF (smaller and higher then median of 5417,1 pg/ml) and B) tissue protein levels of follistatin (smaller and higher then median of 557,7 pg/ml) (n = 58; p < 0.05).
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Fig1: Prognostic cytokines in the tissue of esophageal cancer patients. Kaplan-Maier plots for overall survival of esophageal cancer patients according to A) tissue protein levels of HGF (smaller and higher then median of 5417,1 pg/ml) and B) tissue protein levels of follistatin (smaller and higher then median of 557,7 pg/ml) (n = 58; p < 0.05).

Mentions: To evaluate the prognostic impact of the angiogenic cytokines, Kaplan-Maier survival analysis were performed for each angiogenic factor with the median as cut-off. In the patients serum no angiogenic cytokine was found to be associated with survival time. In the tissue samples HGF and Follistatin levels were associated with patients’ prognosis (p = 0.037; p = 0.036) (Figures 1A and B). Median survival of patients with lower levels of HGF was not reached at time of analysis, while median survival of patients with higher levels was 20.3 ± 4,3 (11,7 – 28,8 95%CI) months. Median survival of patients with lower levels of Follistatin was 36,7 months (95% CI not reached), compared to 16,0 ± 2,7 (10,6 – 21,4 95% CI) months for patients with higher levels. The median survival and the significant cytokines for all patients are presented in Tables 5 and 6. When performing multivariate cox regression analysis including all angiogenic factors in tissue, Follitstatin levels remained associated to overall survival (p = 0.04).Figure 1


Association of angiogenic factors with prognosis in esophageal cancer.

Dreikhausen L, Blank S, Sisic L, Heger U, Weichert W, Jäger D, Bruckner T, Giese N, Grenacher L, Falk C, Ott K, Schmidt T - BMC Cancer (2015)

Prognostic cytokines in the tissue of esophageal cancer patients. Kaplan-Maier plots for overall survival of esophageal cancer patients according to A) tissue protein levels of HGF (smaller and higher then median of 5417,1 pg/ml) and B) tissue protein levels of follistatin (smaller and higher then median of 557,7 pg/ml) (n = 58; p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362831&req=5

Fig1: Prognostic cytokines in the tissue of esophageal cancer patients. Kaplan-Maier plots for overall survival of esophageal cancer patients according to A) tissue protein levels of HGF (smaller and higher then median of 5417,1 pg/ml) and B) tissue protein levels of follistatin (smaller and higher then median of 557,7 pg/ml) (n = 58; p < 0.05).
Mentions: To evaluate the prognostic impact of the angiogenic cytokines, Kaplan-Maier survival analysis were performed for each angiogenic factor with the median as cut-off. In the patients serum no angiogenic cytokine was found to be associated with survival time. In the tissue samples HGF and Follistatin levels were associated with patients’ prognosis (p = 0.037; p = 0.036) (Figures 1A and B). Median survival of patients with lower levels of HGF was not reached at time of analysis, while median survival of patients with higher levels was 20.3 ± 4,3 (11,7 – 28,8 95%CI) months. Median survival of patients with lower levels of Follistatin was 36,7 months (95% CI not reached), compared to 16,0 ± 2,7 (10,6 – 21,4 95% CI) months for patients with higher levels. The median survival and the significant cytokines for all patients are presented in Tables 5 and 6. When performing multivariate cox regression analysis including all angiogenic factors in tissue, Follitstatin levels remained associated to overall survival (p = 0.04).Figure 1

Bottom Line: No significant difference was found in survival between SCC and AEG (p = 0.90). 26 patients were histopathological responders.Angiogenic factors were associated with the following clinicopathological factors: tumor tissue expression of Angiopoietin-2 and Follistatin was higher in SCC compared to AEG (p = 0.022 and p = 0.001).No association with prognosis was found in the patients' serum.

View Article: PubMed Central - PubMed

Affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. lena.dreikhausen@tesionmail.de.

ABSTRACT

Background: Despite multimodal therapy esophageal cancer often presents with poor prognosis. To improve outcome, tumor angiogenesis and anti-angiogenic therapeutic agents have recently gained importance. However, patient subgroups who benefit from anti-angiogenic therapy are not yet defined. In this retrospective exploratory study we investigated 9 angiogenic factors in patients' serum and tissue samples with regard to their association with clinicopathological parameters, prognosis and response in patients with locally advanced preoperatively treated esophageal cancer.

Methods: From 2007 to 2012 preoperative serum and corresponding tumor tissue (n = 54), only serum (n = 20) or only tumor tissue (n = 4) were collected from esophageal squamous cell carcinoma (SCC) (n = 34) and adenocarcinoma of the esophagogastric junction (AEG) (n = 44) staged cT3/4NanyM0/x after preoperative chemo(radio)therapy. Angiogenic cytokine levels in both tissue and serum were measured by multiplex immunoassay.

Results: Median survival in all patients was 28.49 months. No significant difference was found in survival between SCC and AEG (p = 0.90). 26 patients were histopathological responders. Histopathological response was associated with prognosis (p = 0.05). Angiogenic factors were associated with the following clinicopathological factors: tumor tissue expression of Angiopoietin-2 and Follistatin was higher in SCC compared to AEG (p = 0.022 and p = 0.001). High HGF and Follistatin expression in the tumor tissue was associated with poor prognosis in all patients (p = 0.037 and p = 0.036). No association with prognosis was found in the patients' serum. Neither patients' serum nor tumor tissue showed an association between angiogenic factors and response to neoadjuvant therapy.

Conclusion: Two angiogenic factors (HGF and Follistatin) in posttherapeutic tumor tissue are associated with prognosis in esophageal cancer patients. Biological differences of AEG and SCC with respect to angiogenesis were evident by the different expression of 2 angiogenic factors. Results are promising and should be pursued prospectively, optimally sequentially pre- and posttherapeutically.

Show MeSH
Related in: MedlinePlus