Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas

Oda, Yoshinao; Schneider‐Stock, Regine; Ryś, Janusz; Gruchała, A; Niezabitowski, A; Roessner, Albert

doi:10.1007/bf01366956

Cited by 14 publications

(6 citation statements)

References 19 publications

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“…They detected MDR1 mRNA expression in 0–66% of the cases. With regard to MRP1 mRNA expression, Oda et al 49 demonstrated its expression in all three synovial sarcomas by the RT‐PCR method within their series of soft‐tissue sarcomas, although this was not a quantitative analysis. Data for MRP2 and MRP3 mRNA expression have never been presented before—not for synovial sarcoma or for soft‐tissue sarcomas.…”

Section: Discussionmentioning

confidence: 99%

Nuclear expression of Y‐box‐binding protein‐1 correlates with P‐glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma

Oda

Ohishi

Saito

et al. 2003

The Journal of Pathology

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116

108

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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.

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Section: Discussionmentioning

confidence: 99%

Nuclear expression of Y‐box‐binding protein‐1 correlates with P‐glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma

Oda

Ohishi

Saito

et al. 2003

The Journal of Pathology

Self Cite

116

108

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“…The expression of MDR proteins in soft tissue sarcoma has been correlated with a worse survival rate (24) or with a higher histologic grade (25). Leiomyosarcomas have been shown to have a weaker response to chemotherapy compared with other histologic types of sarcoma (26).…”

Section: Discussionmentioning

confidence: 99%

“…The protein concentration of the supernatants was determined using Bradford solution and was normalized. Total lysates were resuspended in Laemmli buffer and 10 Ag of proteins were subjected to SDS-PAGE (8%) under reducing conditions in 25 by densitometry using Scion Image program and analyzed using Excel software (Microsoft, Courtaboeuf, France). The ABCB1 and ABCC1 signals in the GIST samples were expressed relative to the signal measured in placenta extracts and ABCC1 colon extracts, respectively.…”

Section: Methodsmentioning

confidence: 99%

Multidrug Resistance Proteins in Gastrointestinal Stromal Tumors: Site-Dependent Expression and Initial Response to Imatinib

Théou

Gil

Devocelle

et al. 2005

Clinical Cancer Research

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Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the digestive tract and respond poorly to chemotherapy. A tyrosine kinase inhibitor treatment, imatinib mesylate, was recently shown to have antitumor effects in metastatic patients. However, this drug is a substrate for multidrug resistance (MDR) proteins. Therefore, we investigated the expression of ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) by Western blotting in 21GISTs and 3 leiomyosarcomas. All the GISTs were positive for either ABCB1 (86% of cases) or ABCC1 expression (62%), but negative for ABCG2. ABCB1was expressed in all gastric GISTs, but in only 67% of nongastric GISTs. By contrast, ABCC1expression was more common in nongastric tumors (78% versus 42%). The levels of these MDR proteins in gastric GISTs were higher for ABCB1 (P = 0.007) and lower for ABCC1 (P = 0.004) compared with nongastric GISTs. We found no correlation between MDR protein expression and the risk assessment. None of the six patients treated with imatinib was resistant, although all were positive for at least one MDR protein. These results confirm that gastric and nongastric GISTs have different biological characteristics and suggest that MDR proteins do not impair the initial response of the tumor to imatinib.

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“…(29) Coexpression of MDR1 and MRP1 mRNA was significantly correlated with tumor grade in STS. (31) We recently demonstrated that P-gp expression is closely correlated with large tumor size and advanced stage. (30) We also found that the expression of MDR1 and MDR3 mRNA in MPNST was significantly higher than in other STS.…”

Section: Multidrug Resistancementioning

confidence: 98%

“…Mixed STS RT-PCR High histological grade (31) YB-1 Synovial sarcoma IHC Poor prognosis, high proliferative rate (32) Embryonal RMS IHC High proliferative rate (33) Adhesion molecule E-Cadherin Synovial sarcoma IHC Poor prognosis (34) α-Catenin Synovial sarcoma IHC Poor prognosis (34) β-Catenin Synovial sarcoma IHC Poor prognosis, high proliferative rate (34) Dysadherin Epithelioid sarcoma IHC Poor prognosis, proximal type (35) Synovial sarcoma IHC Poor prognosis (36) doi: 10.1111/j.1349-7006.2008.01024.x © 2008 Japanese Cancer Association of p53 and MDM2 protein expression in the same tumor are of high prognostic relevance in mixed-type STS. (9) High MDM2 mRNA level has also been reported as a predictive adverse prognostic factor.…”

Section: Ss18-ssx1mentioning

confidence: 99%

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

Oda

Tsuneyoshi

2009

Cancer Science

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In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18-SSX, EWS-FLI1, and PAX3-FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1 tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200-208) S oft tissue sarcomas are relatively rare malignant neoplasms compared with carcinomas and other neoplasms, and they constitute less than 1% of all cancers. STS are composed of many histological subtypes, such as pleomorphic undifferentiated sarcoma or malignant fibrous histiocytoma, leiomayosarcoma, and liposarcoma. In addition to their wide variety of subtypes, it is often difficult to make an accurate histological diagnosis because certain kinds of STS share similar morphological features. However, it is important to make a definitive diagnosis so that adequate therapy can be administered in each case. Recently, several reciprocal chromosomal translocations and fusion transcripts have been proven to be characteristic of particular histological types (Table 1; Fig. 1). The detection of these fusion transcripts is useful for the differential diagnosis of histologically peculiar cases.In relapsed cases of STS complete remission is difficult, despite the conventional multidisciplinary therapy. Therefore, novel therapies such as molecular target therapy are required, especially in relapsed cases. Several investigators have analyzed tumor-...

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Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas

Cited by 14 publications

References 19 publications

Nuclear expression of Y‐box‐binding protein‐1 correlates with P‐glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma

Nuclear expression of Y‐box‐binding protein‐1 correlates with P‐glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma

Multidrug Resistance Proteins in Gastrointestinal Stromal Tumors: Site-Dependent Expression and Initial Response to Imatinib

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

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