title: Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma.
abstract: Nuclear expression of the Y-box-binding protein (YB-1) has been reported to correlate with the expression of P-glycoprotein in breast cancer and osteosarcoma. Overexpression of the ATP-binding cassette (ABC) superfamily, such as P-glycoprotein/multi-drug resistance (MDR) 1 and MDR-associated protein (MRP) 1, 2 and 3, has been reported in various malignant neoplasms. Fifty-four surgically resected synovial sarcomas were examined immunohistochemically for nuclear expression of YB-1 and intrinsic expression of P-glycoprotein, MRP1, MRP2, and topoisomerase II alpha, and the findings were compared with clinicopathological parameters, proliferative activities as evaluated by MIB-1 labelling index (LI), and the patients' prognoses. In addition, MDR1, MRP1, MRP2, and MRP3 mRNA levels were assessed using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method in 22 concordant frozen specimens from these cases and the findings were compared with six control skeletal muscle tissues. Independent prognostic factors were investigated using the Cox proportional hazards regression model. Nuclear expression of YB-1 protein correlated with P-glycoprotein expression (p = 0.0126). Moreover, cases with nuclear expression of YB-1 correlated with poor survival (p = 0.0495) and showed a high topoisomerase II alpha labelling index (topo II alpha LI) (p = 0.0056) and a high MIB-1 LI (p = 0.01). Multivariate Cox analysis showed that only the nuclear expression of YB-1 (p = 0.0136) and high American Joint Committee on Cancer (AJCC) stage (ie stage III or IV) (p < 0.0001) were independent factors for poor prognosis, while the expression of the YB-1 responsive gene products examined was not. These results indicate that the nuclear expression of YB-1 protein is associated with P-glycoprotein expression and proliferative activity as shown by the topo II alpha LI and the MIB-1 LI, and that expression of this protein is an important independent prognostic factor in synovial sarcoma.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohishi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Eiji
authors.initials: E
authors.lastname: Hinoshita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.forename: Naoko
authors.initials: N
authors.lastname: Kinukawa
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000032:analysis; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002467:Cell Nucleus; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020014:K562 Cells; D026901:Membrane Transport Proteins; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C000715087:ABCC2 protein, human; C070856:YBX1 protein, human; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1