title: PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.
abstract: Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis.
authors.affiliation: Department of Medical Oncology, University Campus Bio-Medico, Roma, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Gaia
authors.initials: G
authors.lastname: Schiavon
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.forename: Marianna
authors.initials: M
authors.lastname: Silletta
authors.forename: Pierfilippo
authors.initials: P
authors.lastname: Crucitti
authors.forename: Paolo
authors.initials: P
authors.lastname: Casali
authors.forename: Angelo P
authors.initials: AP
authors.lastname: Dei Tos
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Badalamenti
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Tomasino
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: James E
authors.initials: JE
authors.lastname: Butrynski
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D000071156:Promyelocytic Leukemia Protein; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D018906:Antineoplastic Agents, Alkylating; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human