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Overexpression of the drug resistance‐associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment
Author(s) -
Grabellus Florian,
Sheu SienYi,
Tötsch Martin,
Lehmann Nils,
Kaiser Gernot M.,
Jasani Bharat,
Taeger Georg,
Schmid Kurt W.
Publication year - 2010
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21513
Subject(s) - medicine , melphalan , sarcoma , immunohistochemistry , soft tissue , pathological , pathology , soft tissue sarcoma , oncology , chemotherapy
Abstract Background and Objectives Hyperthermic isolated limb perfusion with TNF‐α 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. J. Surg. Oncol. 2010; 101:465–470. © 2010 Wiley‐Liss, Inc.