High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease

Brittney Schultz; Daniel D. Miller; Todd DeFor; Bruce R. Blazar; Angela Panoskaltsis-Mortari; Brian C. Betts; Margaret L. MacMillan; Daniel J. Weisdorf; Shernan G. Holtan

doi:10.1111/cup.14218

High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease

Brittney Schultz, Daniel D. Miller, Todd DeFor, Bruce R. Blazar, Angela Panoskaltsis-Mortari, Brian C. Betts, Margaret L. MacMillan, Daniel J. Weisdorf, Shernan G. Holtan

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

BACKGROUND: Amphiregulin (AREG) is increased in circulation in acute graft-versus-host disease (aGVHD) and is associated with poor steroid response and lower survival. The expression of AREG in aGVHD target organs and its association with clinical outcomes are unknown.

METHODS: We performed AREG immunohistochemical staining on skin specimens from 67 patients with aGVHD between the years 2010 and 2015. Two blinded reviewers assessed AREG expression and scored specimens with a semiquantitative scale ranging from 0 (absent) to 4 (most intense).

RESULTS: Median AREG score of aGVHD cases was 3. Sixteen of 67 (23.9%) aGVHD cases had an AREG >3. High skin AREG expression (>3 vs. ≤3) was associated with increased overall clinical grade of aGVHD (52.9% vs. 33.4% clinical grade III-IV, p = 0.02), reduced 3-year overall survival (OS; 13% vs. 61%, p < 0.01), and increased 3-year non-relapse mortality (NRM; 56% vs. 20%, p = 0.05).

CONCLUSION: High skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor OS, and increased NRM.

Original language	English (US)
Pages (from-to)	532-535
Number of pages	4
Journal	Journal of cutaneous pathology
Volume	49
Issue number	6
DOIs	https://doi.org/10.1111/cup.14218
State	Published - Jun 2022

Bibliographical note

Funding Information:
Masonic Cancer Center Pilot Grant program (SGH) and Marrow on the Move (SGH); Women's Early Research Career Award, the Department of Medicine, University of Minnesota Funding information

Publisher Copyright:
© 2022 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.

Keywords

acute GVHD
allogeneic hematopoietic cell transplantation
amphiregulin
epidermal growth factor

PubMed: MeSH publication types

Journal Article

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10.1111/cup.14218

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title = "High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease",

abstract = "BACKGROUND: Amphiregulin (AREG) is increased in circulation in acute graft-versus-host disease (aGVHD) and is associated with poor steroid response and lower survival. The expression of AREG in aGVHD target organs and its association with clinical outcomes are unknown.METHODS: We performed AREG immunohistochemical staining on skin specimens from 67 patients with aGVHD between the years 2010 and 2015. Two blinded reviewers assessed AREG expression and scored specimens with a semiquantitative scale ranging from 0 (absent) to 4 (most intense).RESULTS: Median AREG score of aGVHD cases was 3. Sixteen of 67 (23.9%) aGVHD cases had an AREG >3. High skin AREG expression (>3 vs. ≤3) was associated with increased overall clinical grade of aGVHD (52.9% vs. 33.4% clinical grade III-IV, p = 0.02), reduced 3-year overall survival (OS; 13% vs. 61%, p < 0.01), and increased 3-year non-relapse mortality (NRM; 56% vs. 20%, p = 0.05).CONCLUSION: High skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor OS, and increased NRM.",

keywords = "acute GVHD, allogeneic hematopoietic cell transplantation, amphiregulin, epidermal growth factor",

author = "Brittney Schultz and Miller, {Daniel D.} and Todd DeFor and Blazar, {Bruce R.} and Angela Panoskaltsis-Mortari and Betts, {Brian C.} and MacMillan, {Margaret L.} and Weisdorf, {Daniel J.} and Holtan, {Shernan G.}",

note = "Funding Information: Masonic Cancer Center Pilot Grant program (SGH) and Marrow on the Move (SGH); Women's Early Research Career Award, the Department of Medicine, University of Minnesota Funding information Publisher Copyright: {\textcopyright} 2022 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.",

year = "2022",

month = jun,

doi = "10.1111/cup.14218",

language = "English (US)",

volume = "49",

pages = "532--535",

journal = "Journal of cutaneous pathology",

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TY - JOUR

T1 - High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease

AU - Schultz, Brittney

AU - Miller, Daniel D.

AU - DeFor, Todd

AU - Blazar, Bruce R.

AU - Panoskaltsis-Mortari, Angela

AU - Betts, Brian C.

AU - MacMillan, Margaret L.

AU - Weisdorf, Daniel J.

AU - Holtan, Shernan G.

N1 - Funding Information: Masonic Cancer Center Pilot Grant program (SGH) and Marrow on the Move (SGH); Women's Early Research Career Award, the Department of Medicine, University of Minnesota Funding information Publisher Copyright: © 2022 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.

PY - 2022/6

Y1 - 2022/6

N2 - BACKGROUND: Amphiregulin (AREG) is increased in circulation in acute graft-versus-host disease (aGVHD) and is associated with poor steroid response and lower survival. The expression of AREG in aGVHD target organs and its association with clinical outcomes are unknown.METHODS: We performed AREG immunohistochemical staining on skin specimens from 67 patients with aGVHD between the years 2010 and 2015. Two blinded reviewers assessed AREG expression and scored specimens with a semiquantitative scale ranging from 0 (absent) to 4 (most intense).RESULTS: Median AREG score of aGVHD cases was 3. Sixteen of 67 (23.9%) aGVHD cases had an AREG >3. High skin AREG expression (>3 vs. ≤3) was associated with increased overall clinical grade of aGVHD (52.9% vs. 33.4% clinical grade III-IV, p = 0.02), reduced 3-year overall survival (OS; 13% vs. 61%, p < 0.01), and increased 3-year non-relapse mortality (NRM; 56% vs. 20%, p = 0.05).CONCLUSION: High skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor OS, and increased NRM.

AB - BACKGROUND: Amphiregulin (AREG) is increased in circulation in acute graft-versus-host disease (aGVHD) and is associated with poor steroid response and lower survival. The expression of AREG in aGVHD target organs and its association with clinical outcomes are unknown.METHODS: We performed AREG immunohistochemical staining on skin specimens from 67 patients with aGVHD between the years 2010 and 2015. Two blinded reviewers assessed AREG expression and scored specimens with a semiquantitative scale ranging from 0 (absent) to 4 (most intense).RESULTS: Median AREG score of aGVHD cases was 3. Sixteen of 67 (23.9%) aGVHD cases had an AREG >3. High skin AREG expression (>3 vs. ≤3) was associated with increased overall clinical grade of aGVHD (52.9% vs. 33.4% clinical grade III-IV, p = 0.02), reduced 3-year overall survival (OS; 13% vs. 61%, p < 0.01), and increased 3-year non-relapse mortality (NRM; 56% vs. 20%, p = 0.05).CONCLUSION: High skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor OS, and increased NRM.

KW - acute GVHD

KW - allogeneic hematopoietic cell transplantation

KW - amphiregulin

KW - epidermal growth factor

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High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease

Abstract

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