title: Overexpression of the drug resistance-associated protein metallothionein does not correlate with response of sarcomas to isolated limb perfusion treatment.
abstract: OBJECTIVE
  Hyperthermic isolated limb perfusion with TNF-alpha 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 <or=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.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Essen and Sarcoma Center at the West German Cancer Center, University of Duisburg-Essen, Essen, Germany. florian.grabellus@uk-essen.de
authors.forename: Florian
authors.initials: F
authors.lastname: Grabellus
authors.forename: Sien-Yi
authors.initials: SY
authors.lastname: Sheu
authors.forename: Martin
authors.initials: M
authors.lastname: Tötsch
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.forename: Gernot M
authors.initials: GM
authors.lastname: Kaiser
authors.forename: Bharat
authors.initials: B
authors.lastname: Jasani
authors.forename: Georg
authors.initials: G
authors.lastname: Taeger
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010478:Chemotherapy, Cancer, Regional Perfusion; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008668:Metallothionein / Q000032:analysis*; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008668:Metallothionein; D008558:Melphalan