Overexpression of the drug resistance-associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment

Florian Grabellus, Sien Yi Sheu, Martin Tötsch, Nils Lehmann, Gernot M. Kaiser, Bharat Jasani, Georg Taeger, Kurt W. Schmid

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and Objectives: Hyperthermic isolated limb perfusion with TNF-a and melphalan (HILP-TM) achieves high response rates in sarcomas. Melphalan resistance was previously reported to be associated with overexpression of metallothioneins (MTs). Objective of this study was to investigate the influence of MT expression on tumor responses in HILP-TM-treated soft tissue (STSs) and bone sarcomas (BS). Methods: In primary biopsies of 41 HILP-TM-treated sarcomas (37 STSs and 4 BS), MT expression was assessed by an immunoreactive score. The pathologic response to HILP-TM was quantified in the corresponding tumor resection specimens. We studied the association of MT-IRS between histological regression (responder >90%, or non-responder ≤90% regression), tumor proliferation, and other clinico-pathological parameters. Results: MT expression was found in 70.7% (N=29) of tumors (high 12.2%, moderate 19.5%, and low 39.0%). After HILP-TM, 20 cases (48.8%) were categorized as " responders" and 21 (51.2%) as "non-responders." Six "responders" (14.6%) presented with complete regression. MT expression positively correlated with tumor proliferation but not with HILP-TM. Conclusions: HILP-TM showed a favorable response in a high rate of sarcomas. Although MT overexpression was observed in this cohort of sarcomas, the immunohistochemical MT status was not predictive of the tumor response after HILP-TM treatment.

Original languageEnglish
Pages (from-to)465-470
Number of pages6
JournalJournal of Surgical Oncology
Volume101
Issue number6
DOIs
Publication statusPublished - May 1 2010
Externally publishedYes

Fingerprint

Melphalan
Metallothionein
Drug Resistance
Sarcoma
Extremities
Perfusion
Proteins
Neoplasms
Sarcoma 37
Biopsy
Bone and Bones

Keywords

  • Isolated limb perfusion
  • Melphalan
  • Metallothionein
  • Sarcoma
  • TNF-α

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Overexpression of the drug resistance-associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment. / Grabellus, Florian; Sheu, Sien Yi; Tötsch, Martin; Lehmann, Nils; Kaiser, Gernot M.; Jasani, Bharat; Taeger, Georg; Schmid, Kurt W.

In: Journal of Surgical Oncology, Vol. 101, No. 6, 01.05.2010, p. 465-470.

Research output: Contribution to journalArticle

Grabellus, Florian ; Sheu, Sien Yi ; Tötsch, Martin ; Lehmann, Nils ; Kaiser, Gernot M. ; Jasani, Bharat ; Taeger, Georg ; Schmid, Kurt W. / Overexpression of the drug resistance-associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment. In: Journal of Surgical Oncology. 2010 ; Vol. 101, No. 6. pp. 465-470.
@article{0b4311fcd72942d8b136eb8139365ac3,
title = "Overexpression of the drug resistance-associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment",
abstract = "Background and Objectives: Hyperthermic isolated limb perfusion with TNF-a and melphalan (HILP-TM) achieves high response rates in sarcomas. Melphalan resistance was previously reported to be associated with overexpression of metallothioneins (MTs). Objective of this study was to investigate the influence of MT expression on tumor responses in HILP-TM-treated soft tissue (STSs) and bone sarcomas (BS). Methods: In primary biopsies of 41 HILP-TM-treated sarcomas (37 STSs and 4 BS), MT expression was assessed by an immunoreactive score. The pathologic response to HILP-TM was quantified in the corresponding tumor resection specimens. We studied the association of MT-IRS between histological regression (responder >90{\%}, or non-responder ≤90{\%} regression), tumor proliferation, and other clinico-pathological parameters. Results: MT expression was found in 70.7{\%} (N=29) of tumors (high 12.2{\%}, moderate 19.5{\%}, and low 39.0{\%}). After HILP-TM, 20 cases (48.8{\%}) were categorized as {"} responders{"} and 21 (51.2{\%}) as {"}non-responders.{"} Six {"}responders{"} (14.6{\%}) presented with complete regression. MT expression positively correlated with tumor proliferation but not with HILP-TM. Conclusions: HILP-TM showed a favorable response in a high rate of sarcomas. Although MT overexpression was observed in this cohort of sarcomas, the immunohistochemical MT status was not predictive of the tumor response after HILP-TM treatment.",
keywords = "Isolated limb perfusion, Melphalan, Metallothionein, Sarcoma, TNF-α",
author = "Florian Grabellus and Sheu, {Sien Yi} and Martin T{\"o}tsch and Nils Lehmann and Kaiser, {Gernot M.} and Bharat Jasani and Georg Taeger and Schmid, {Kurt W.}",
year = "2010",
month = "5",
day = "1",
doi = "10.1002/jso.21513",
language = "English",
volume = "101",
pages = "465--470",
journal = "Journal of Surgical Oncology",
issn = "0022-4790",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Overexpression of the drug resistance-associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment

AU - Grabellus, Florian

AU - Sheu, Sien Yi

AU - Tötsch, Martin

AU - Lehmann, Nils

AU - Kaiser, Gernot M.

AU - Jasani, Bharat

AU - Taeger, Georg

AU - Schmid, Kurt W.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Background and Objectives: Hyperthermic isolated limb perfusion with TNF-a and melphalan (HILP-TM) achieves high response rates in sarcomas. Melphalan resistance was previously reported to be associated with overexpression of metallothioneins (MTs). Objective of this study was to investigate the influence of MT expression on tumor responses in HILP-TM-treated soft tissue (STSs) and bone sarcomas (BS). Methods: In primary biopsies of 41 HILP-TM-treated sarcomas (37 STSs and 4 BS), MT expression was assessed by an immunoreactive score. The pathologic response to HILP-TM was quantified in the corresponding tumor resection specimens. We studied the association of MT-IRS between histological regression (responder >90%, or non-responder ≤90% regression), tumor proliferation, and other clinico-pathological parameters. Results: MT expression was found in 70.7% (N=29) of tumors (high 12.2%, moderate 19.5%, and low 39.0%). After HILP-TM, 20 cases (48.8%) were categorized as " responders" and 21 (51.2%) as "non-responders." Six "responders" (14.6%) presented with complete regression. MT expression positively correlated with tumor proliferation but not with HILP-TM. Conclusions: HILP-TM showed a favorable response in a high rate of sarcomas. Although MT overexpression was observed in this cohort of sarcomas, the immunohistochemical MT status was not predictive of the tumor response after HILP-TM treatment.

AB - Background and Objectives: Hyperthermic isolated limb perfusion with TNF-a and melphalan (HILP-TM) achieves high response rates in sarcomas. Melphalan resistance was previously reported to be associated with overexpression of metallothioneins (MTs). Objective of this study was to investigate the influence of MT expression on tumor responses in HILP-TM-treated soft tissue (STSs) and bone sarcomas (BS). Methods: In primary biopsies of 41 HILP-TM-treated sarcomas (37 STSs and 4 BS), MT expression was assessed by an immunoreactive score. The pathologic response to HILP-TM was quantified in the corresponding tumor resection specimens. We studied the association of MT-IRS between histological regression (responder >90%, or non-responder ≤90% regression), tumor proliferation, and other clinico-pathological parameters. Results: MT expression was found in 70.7% (N=29) of tumors (high 12.2%, moderate 19.5%, and low 39.0%). After HILP-TM, 20 cases (48.8%) were categorized as " responders" and 21 (51.2%) as "non-responders." Six "responders" (14.6%) presented with complete regression. MT expression positively correlated with tumor proliferation but not with HILP-TM. Conclusions: HILP-TM showed a favorable response in a high rate of sarcomas. Although MT overexpression was observed in this cohort of sarcomas, the immunohistochemical MT status was not predictive of the tumor response after HILP-TM treatment.

KW - Isolated limb perfusion

KW - Melphalan

KW - Metallothionein

KW - Sarcoma

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=77950849840&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950849840&partnerID=8YFLogxK

U2 - 10.1002/jso.21513

DO - 10.1002/jso.21513

M3 - Article

VL - 101

SP - 465

EP - 470

JO - Journal of Surgical Oncology

JF - Journal of Surgical Oncology

SN - 0022-4790

IS - 6

ER -