title: Expression of MSH2 and MSH6 on a tissue microarray in patients with osteosarcoma.
abstract: OBJECTIVE
  Reliable prognostic factors for the outcome of patients with osteosarcoma (OS) remain elusive. We analyzed the relationship between immunohistochemical expression of deoxyribonucleic acid (DNA) mismatch repair (MMR) proteins, MutS protein homolog 2 (MSH2) and MSH6 using a tissue microarray (TMA) with respect to OS patient demographics and survival time.
  
  
  METHODS
  We retrieved tumor tissue specimens from bone tissue originating from surgical primary tumor specimens of OS patients to generate a TMA and stained sections with antibodies against MSH2 and MSH6.
  
  
  RESULTS
  Tumor resections of 67 patients with a mean follow-up of 98 months were evaluated. MSH2 was expressed in nine (13%), MSH6 in ten (15%) and combined MSH2 and MSH6 (MSH2/6) in six (9%) patients. Significantly shorter survival times were associated with expression of MSH6, MSH2/6, as well as simultaneous non-response to chemotherapy and presence of metastasis.
  
  
  CONCLUSIONS
  The survival time of patients with OS may be predicted by local expression of MSH6 and MSH2/6 in surgical primary tumor resections. This study shows the prognostic value of the local expression of DNA MMR proteins, as markers for poor prognosis of OS patients.
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zürich, Switzerland Division of Trauma Surgery, Department of Surgery, University Hospital Zürich, Zürich, Switzerland thorsten.jentzsch@usz.ch.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Jentzsch
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zürich, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Robl
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zürich, Switzerland.
authors.forename: Maren
authors.initials: M
authors.lastname: Husmann
authors.affiliation: Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Beata
authors.initials: B
authors.lastname: Bode-Lesniewska
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zürich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fuchs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis*; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein
keywords: MSH2; MSH2/6 TMA; MSH6; Osteosarcoma; chemotherapy responder; demographics; metastasis; survival