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Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer.

Wallin U, Glimelius B, Jirström K, Darmanis S, Nong RY, Pontén F, Johansson C, Påhlman L, Birgisson H - Br. J. Cancer (2011)

Bottom Line: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51).Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

View Article: PubMed Central - PubMed

Affiliation: Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, 2800 Medical Building, 2800 Chicago Avenue South, Suite 300, Minneapolis, MN, USA. ulrik.wallin@surgsci.uu.se

ABSTRACT

Background: Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC).

Methods: Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay.

Results: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).

Conclusion: Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

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Related in: MedlinePlus

These images represent the four levels of the intensity of immunoreactivity, resulting from immunostaining with GDF15 antibody on primary colorectal cancer tissues. Negative (A), weak (B), moderate (C) and strong intensity staining (D). Images with immunostaining present had 25–75% fraction of positive cells.
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fig1: These images represent the four levels of the intensity of immunoreactivity, resulting from immunostaining with GDF15 antibody on primary colorectal cancer tissues. Negative (A), weak (B), moderate (C) and strong intensity staining (D). Images with immunostaining present had 25–75% fraction of positive cells.

Mentions: Immunohistochemistry was performed on 4 μm TMA sections using HPA011191 (Atlas Antibodies, Stockholm, Sweden) as primary antibody to detect GDF15. Automated immunohistochemistry (Autostainer 480, Lab Vision, Fremont, CA, USA) was performed as previously described (Paavilainen et al, 2010). Immunohistochemically stained TMA sections were scanned in high-resolution scanners (ScanScope T2, Aperio Technologies, Vista, CA, USA) and separated into individual spot images representing different cores in the TMAs. The annotation process included estimation of the intensity of immunoreactivity for GDF15 (negative (0), weak (1), moderate (2), or strong, (3) and fraction (%) of GDF15-positive cells (<1% (0), 1–24% (1), 25–75% (2), or >75% (3)) (Figure 1). Tumours with no (0) or low (1) intensity and no (0) or low (1) fraction of GDF15 expression were allocated to one group and tumours with moderate (2) or high (3) intensity and moderate (2) and high (3) fraction of GDF15 expression were allocated into a second group.


Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer.

Wallin U, Glimelius B, Jirström K, Darmanis S, Nong RY, Pontén F, Johansson C, Påhlman L, Birgisson H - Br. J. Cancer (2011)

These images represent the four levels of the intensity of immunoreactivity, resulting from immunostaining with GDF15 antibody on primary colorectal cancer tissues. Negative (A), weak (B), moderate (C) and strong intensity staining (D). Images with immunostaining present had 25–75% fraction of positive cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101900&req=5

fig1: These images represent the four levels of the intensity of immunoreactivity, resulting from immunostaining with GDF15 antibody on primary colorectal cancer tissues. Negative (A), weak (B), moderate (C) and strong intensity staining (D). Images with immunostaining present had 25–75% fraction of positive cells.
Mentions: Immunohistochemistry was performed on 4 μm TMA sections using HPA011191 (Atlas Antibodies, Stockholm, Sweden) as primary antibody to detect GDF15. Automated immunohistochemistry (Autostainer 480, Lab Vision, Fremont, CA, USA) was performed as previously described (Paavilainen et al, 2010). Immunohistochemically stained TMA sections were scanned in high-resolution scanners (ScanScope T2, Aperio Technologies, Vista, CA, USA) and separated into individual spot images representing different cores in the TMAs. The annotation process included estimation of the intensity of immunoreactivity for GDF15 (negative (0), weak (1), moderate (2), or strong, (3) and fraction (%) of GDF15-positive cells (<1% (0), 1–24% (1), 25–75% (2), or >75% (3)) (Figure 1). Tumours with no (0) or low (1) intensity and no (0) or low (1) fraction of GDF15 expression were allocated to one group and tumours with moderate (2) or high (3) intensity and moderate (2) and high (3) fraction of GDF15 expression were allocated into a second group.

Bottom Line: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51).Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

View Article: PubMed Central - PubMed

Affiliation: Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, 2800 Medical Building, 2800 Chicago Avenue South, Suite 300, Minneapolis, MN, USA. ulrik.wallin@surgsci.uu.se

ABSTRACT

Background: Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC).

Methods: Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay.

Results: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).

Conclusion: Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

Show MeSH
Related in: MedlinePlus