Prognostic and predictive value of YKL-40 in stage IIB-III melanoma

Merete Krogh, Ib Christensen, Marna Bouwhuis, Julia S Johansen, Peter Nørgaard, Henrik Schmidt, Johan Hansson, Stefan Suciu, Alexander M M Eggermont, Lars Bastholt, Nordic Melanoma Group and EORTC Melanoma Group

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.

OriginalsprogEngelsk
TidsskriftMelanoma Research
Vol/bind26
Udgave nummer4
Sider (fra-til)367-376
ISSN0960-8931
DOI
StatusUdgivet - 2016

Fingeraftryk

Melanoma
Confidence Intervals
Macrophages
Observation
Neoplasms
Lymph Nodes
Serum
Research
Multivariate Analysis
Proteins

Citer dette

Krogh, M., Christensen, I., Bouwhuis, M., Johansen, J. S., Nørgaard, P., Schmidt, H., ... Nordic Melanoma Group and EORTC Melanoma Group (2016). Prognostic and predictive value of YKL-40 in stage IIB-III melanoma. Melanoma Research, 26(4), 367-376. https://doi.org/10.1097/CMR.0000000000000237
Krogh, Merete ; Christensen, Ib ; Bouwhuis, Marna ; Johansen, Julia S ; Nørgaard, Peter ; Schmidt, Henrik ; Hansson, Johan ; Suciu, Stefan ; Eggermont, Alexander M M ; Bastholt, Lars ; Nordic Melanoma Group and EORTC Melanoma Group. / Prognostic and predictive value of YKL-40 in stage IIB-III melanoma. I: Melanoma Research. 2016 ; Bind 26, Nr. 4. s. 367-376.
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abstract = "This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95{\%} confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95{\%} CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95{\%} CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95{\%} CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.",
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author = "Merete Krogh and Ib Christensen and Marna Bouwhuis and Johansen, {Julia S} and Peter N{\o}rgaard and Henrik Schmidt and Johan Hansson and Stefan Suciu and Eggermont, {Alexander M M} and Lars Bastholt and {Nordic Melanoma Group and EORTC Melanoma Group}",
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Krogh, M, Christensen, I, Bouwhuis, M, Johansen, JS, Nørgaard, P, Schmidt, H, Hansson, J, Suciu, S, Eggermont, AMM, Bastholt, L & Nordic Melanoma Group and EORTC Melanoma Group 2016, 'Prognostic and predictive value of YKL-40 in stage IIB-III melanoma', Melanoma Research, bind 26, nr. 4, s. 367-376. https://doi.org/10.1097/CMR.0000000000000237

Prognostic and predictive value of YKL-40 in stage IIB-III melanoma. / Krogh, Merete; Christensen, Ib; Bouwhuis, Marna; Johansen, Julia S; Nørgaard, Peter; Schmidt, Henrik; Hansson, Johan; Suciu, Stefan; Eggermont, Alexander M M; Bastholt, Lars; Nordic Melanoma Group and EORTC Melanoma Group.

I: Melanoma Research, Bind 26, Nr. 4, 2016, s. 367-376.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Prognostic and predictive value of YKL-40 in stage IIB-III melanoma

AU - Krogh, Merete

AU - Christensen, Ib

AU - Bouwhuis, Marna

AU - Johansen, Julia S

AU - Nørgaard, Peter

AU - Schmidt, Henrik

AU - Hansson, Johan

AU - Suciu, Stefan

AU - Eggermont, Alexander M M

AU - Bastholt, Lars

AU - Nordic Melanoma Group and EORTC Melanoma Group

PY - 2016

Y1 - 2016

N2 - This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.

AB - This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.

KW - Journal Article

U2 - 10.1097/CMR.0000000000000237

DO - 10.1097/CMR.0000000000000237

M3 - Journal article

C2 - 27076041

VL - 26

SP - 367

EP - 376

JO - Melanoma Research

JF - Melanoma Research

SN - 0960-8931

IS - 4

ER -