Nuclear expression of Y-box-binding protein-I correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma

Yoshinao Oda, Yoshihiro Ohishi, Tsuyoshi Saito, Eiji Hinoshita, Takeshi Uchiumi, Naoko Kinukawa, Yukihide Iwamoto, Kimitoshi Kohno, Michihiko Kuwano, Masazumi Tsuneyoshi

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98 Citations (Scopus)

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 α, 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 α labelling index (topo II α 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 α LI and the MIB-1 LI, and that expression of this protein is an important independent prognostic factor in synovial sarcoma.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalJournal of Pathology
Volume199
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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