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Wilms’ tumour gene 1 (WT1) is a new prognostic marker in high grade uterine sarcoma

Wilms’ tumour gene 1 (WT1) is a new prognostic marker in high grade uterine sarcoma . A. Coosemans, B. Van Calster, L. Verbist, Ph. Moerman, I. Vergote, S.W. Van Gool, F. Amant. Laboratory of Experimental Gynaecology and Immunology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Belgium

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Wilms’ tumour gene 1 (WT1) is a new prognostic marker in high grade uterine sarcoma

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  1. Wilms’ tumour gene 1 (WT1) is a new prognostic marker in high grade uterine sarcoma A. Coosemans, B. Van Calster, L. Verbist, Ph. Moerman, I. Vergote, S.W. Van Gool, F. Amant Laboratory of Experimental Gynaecology and Immunology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Belgium Department of Electric Engineering (ESAT), Katholieke Universiteit Leuven, Belgium Department of human pathology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Belgium

  2. Background (1) • WT1 : Wilms’ tumour gene 1 • located on #11p13 • 1990 : discovered in Wilms tumour (paediatric kidney cancer) • Complex molecular function : transcription and translation on DNA and RNA level • Role : • Embryogenic : role in development of urogenital system, central nervous system, heart, blood • Adult life : role in carcinogenesis – overexpression of wild type in several haematological and solid malignancies • Depending on the type of tumour : behaviour as a oncogene or supressor gene

  3. Background (2) • Uterine sarcoma : • Rare type of uterine tumour • 4 subtypes : • Carcinosarcoma (CS), leiomyosarcoma (LMS), undifferentiated sarcoma (US) : high grade • Endometrial stromal sarcoma (ESS) : low grade • Poor prognosis : 5 year survival : • Stage I-II : 50% • Stage III-IV : 10% • Surgery is the corner stone - no clear benefits from adjuvant therapy in early stages – shortlasting therapeutic options in advanced stages

  4. Background (3) • WT1 and uterine sarcoma

  5. Materials and methods (1) • 54 women with high grade uterine sarcoma • Follow up of at least 12 months

  6. Materials and methods (2) • IMMUNOHISTOCHEMISTRY • WT1 immunohistochemistry on 1 slide of each tumour (monoclonal mouse anti-human Wilms’ Tumor 1 clone 6F-H2 (DAKO)) • STATISTICAL ANALYSIS • Survival curves by Kaplan Meier • Univariate and multivariate analysis by Cox regression analysis

  7. Materials and methods (3) • 1984-2008 : 26 studies on prognosis in uterine sarcoma, including multivariate analysis in more than 40 patients • Most frequently studied parameters : • Stage : 24 studies • Age : 23 studies • Grade : 15 studies • Subtype : 11 studies • Menopauzal status : 10 studies • Size : 9 studies • Mitotic index : 8 studies • Adjuvant therapy : 6 studies

  8. Results (1)

  9. Results (2) : univariate analysis Kaplan Meier survival curves

  10. Results (3) : univariate analysis LR p=0,0058 LR p <0,0001

  11. Results (4) : multivariate analysis PFS OS

  12. Conclusion • WT1 independently worsens the prognosis of uterine sarcoma • The stronger the WT1 expression, the worse the prognosis • Similar observations have been made in breast carcinoma (Miyoshi, 2002), leukaemia (Inoue, 1994) and hepatocellular carcinoma (Sera, 2008)

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