CYP3A isoforms in Ewing's sarcoma tumours

an immunohistochemical study with clinical correlation

Hamid Zia, Graeme I Murray, Carrie A Vyhlidal, J Steven Leeder, Ahmed E Anwar, Marilyn M Bui, Atif A Ahmed

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Ewing's sarcoma family tumour is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma family tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalInternational journal of experimental pathology
Volume96
Issue number2
Early online date9 Feb 2015
DOIs
Publication statusPublished - Apr 2015

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Cytochrome P-450 CYP3A
Ewing's Sarcoma
Protein Isoforms
Neoplasms
Neoplasm Metastasis
Clinical Studies
Staining and Labeling
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Disease-Free Survival
Biomarkers

Keywords

  • CYP3A4
  • cytochrome P450
  • Ewing's sarcoma
  • Immunohistochemistry

Cite this

CYP3A isoforms in Ewing's sarcoma tumours : an immunohistochemical study with clinical correlation. / Zia, Hamid; Murray, Graeme I; Vyhlidal, Carrie A; Leeder, J Steven; Anwar, Ahmed E; Bui, Marilyn M; Ahmed, Atif A.

In: International journal of experimental pathology, Vol. 96, No. 2, 04.2015, p. 81-86.

Research output: Contribution to journalArticle

Zia, Hamid ; Murray, Graeme I ; Vyhlidal, Carrie A ; Leeder, J Steven ; Anwar, Ahmed E ; Bui, Marilyn M ; Ahmed, Atif A. / CYP3A isoforms in Ewing's sarcoma tumours : an immunohistochemical study with clinical correlation. In: International journal of experimental pathology. 2015 ; Vol. 96, No. 2. pp. 81-86.
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abstract = "Ewing's sarcoma family tumour is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81{\%}) cases with high expression noted in 13 (40{\%}) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6{\%}, 40.6{\%}). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma family tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.",
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note = "{\circledC} 2015 The Authors. International Journal of Experimental Pathology {\circledC} 2015 International Journal of Experimental Pathology. Acknowledgement Hamid Zia: Performed research analysis and drafted initial manuscript Graeme Murray: Performed essential experiments Carrie Vyhlidal: Supplied essential reagents Steven Leeder: Supplied essential reagents Ahmed Anwar: Performed biostatistical analysis Marilyn Bui: Supplied patients data and materials Atif Ahmed: Designed research concept, analyzed data and finalized the manuscript.",
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T1 - CYP3A isoforms in Ewing's sarcoma tumours

T2 - an immunohistochemical study with clinical correlation

AU - Zia, Hamid

AU - Murray, Graeme I

AU - Vyhlidal, Carrie A

AU - Leeder, J Steven

AU - Anwar, Ahmed E

AU - Bui, Marilyn M

AU - Ahmed, Atif A

N1 - © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology. Acknowledgement Hamid Zia: Performed research analysis and drafted initial manuscript Graeme Murray: Performed essential experiments Carrie Vyhlidal: Supplied essential reagents Steven Leeder: Supplied essential reagents Ahmed Anwar: Performed biostatistical analysis Marilyn Bui: Supplied patients data and materials Atif Ahmed: Designed research concept, analyzed data and finalized the manuscript.

PY - 2015/4

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N2 - Ewing's sarcoma family tumour is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma family tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.

AB - Ewing's sarcoma family tumour is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma family tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.

KW - CYP3A4

KW - cytochrome P450

KW - Ewing's sarcoma

KW - Immunohistochemistry

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VL - 96

SP - 81

EP - 86

JO - International journal of experimental pathology

JF - International journal of experimental pathology

SN - 0959-9673

IS - 2

ER -