title: Diagnostic use of fluorescence in situ hybridization in expert review in a phase 2 study of trabectedin monotherapy in patients with advanced, translocation-related sarcoma.
abstract: BACKGROUND
  Fluorescence in situ hybridization (FISH) is one of the most powerful genetic analysis tools for pathological diagnoses. FISH can detect various genetic abnormalities including gene translocation that was specifically found in translocation-related sarcomas (TRSs). Here, we report the use of FISH in expert review in a phase 2 study of trabectedin monotherapy for patients with advanced TRS.
  
  
  METHODS
  TRS patients (n = 76) were enrolled in the trial at 12 study sites after pathological diagnoses were made, including morphological examination with or without evidence of translocation by genetic testing. Following histological reviews of the representative specimens at the study sites, we performed immunohistochemistry using the appropriate antibodies and FISH for genetic confirmation of the tumor types in the expert review.
  
  
  RESULTS
  Among the 76 TRS cases, no split signal for SS18 probe was detected by FISH in three synovial sarcoma cases that were diagnosed at the study sites. Malignant peripheral nerve sheath tumor (MPNST) was diagnosed in two cases and sarcomatoid carcinoma in one. One of the cases was a small round cell variant of MPNST. After excluding these three cases, we assessed the other 73. There were no split signals detected in 7 of the 73 cases by FISH analysis, due to decalcification and hyperfixation procedures. Excluding these seven cases, FISH detected translocations in 95 % (63/66) of the study cases with a high sensitivity.
  
  
  CONCLUSIONS
  The diagnosis of TRS by FISH was highly sensitive and enabled genetic confirmation of the pathological diagnoses. We strongly recommend FISH as a confirmatory diagnostic test for TRS, which would enable the selection of patients with TRS in whom trabectedin is expected to be effective. This study was done in part that registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan. ssugita@sapmed.ac.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sugita
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004149:Dioxoles / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D010641:Phenotype; D011237:Predictive Value of Tests; D012509:Sarcoma / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D013997:Time Factors; D000077606:Trabectedin; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
keywords: Fluorescence in situ hybridization; Immunohistochemistry; Malignant peripheral nerve sheath tumor; Sarcomatoid carcinoma; Synovial sarcoma; Translocation-related sarcoma