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Meme kanserinde Wilms Tümör 1 (WT1) protein ekspresyonunun prognostik önemi

Year 2011, Volume: 17 Issue: 2, 67 - 72, 01.03.2011

Abstract

Breast cancer is the most common cancer among women all over the world. Since the clinical outcome of breast cancer may differ among some women who have the same clinicopathological stage, researchers focused on additional prognostic parameters to predict the tumor behavior. The aim of this study was to investigate the prognostic value of Wilms Tumor 1 (WT1) expression in tumor tissues and to compare it with known prognostic variables in patients with breast cancer. In patients with breast cancer, we investigated the relationship between (WT1) protein expression in tumor and surrounding tissues and prognostic variables including age, pathologic type, axillary node involvement, estrogen receptor (ER) status, menopausal status, stage (TNM), tumor grade and treatment. Borderline significance was detected between WT1 monoclonal antibody (mAb) staining and premenopausal state (p=0.051). Additionally, surrounding tissue staining showed significant correlations with grade (p=0.045), stage (p=0.026), lymph node status (p=0.026), and axillary involvement (p=0.02), respectively. No correlation was demonstrated between relapse free survival, relapse sites and WT1 mAb staining of tumor and surrounding tissues (p=0.36). WT1 mAb staining was demonstrated in human breast cancer tissues, and in this study we have used monoclonal antibody against WT1 on paraffin-embedded tissue samples. The results indicate that WT1 expression by tumor is more evident in premenopausal state rather than postmenopausal period. To confirm the results, we need large scale studies on WT1 expression in breast cancer.

References

  • 1. Gillmore R, Xue SA, Holler A, Kaeda J, Hadjiminas D, Healy V, et al. Detection of Wilms' tumor antigen--specific CTL in tumor-draining lymph nodes of patients with early breast cancer. Clin Cancer Res 2006;12(1):34-42
  • 2. Fisher B, Osborne CK, Margolese RG, Bloomer WD. Neoplasm of the breast. In: Holland JF, Bast RC Jr, Morton DL, Frei E III, Kufe DW, Weichselbaum RR (eds). Cancer Medicine,Williams and Wilkins Co: International Edition, 1997: 2362-6
  • 3. Hennessy C, Henry JA, May FE, Westley BR, Angus B, Lennard TW. Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. J Natl Cancer Inst 1991;83(4):281-5
  • 4. Nemoto T, Natarajan N, Bedwani R, Vana J, Murphy GP
  • Breast cancer in the medial half. Results of the 1978 national survey of the American College of Surgeons. Cancer 1983;51(8):1333-8
  • 5. Sauer T, Furu I, Beraki K, Jebsen PW, Ormerod E, Naess O
  • nm23 protein expression in fine needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status and ploidy. Cancer 1998;84(2):109-14
  • 6. Thompson AM, Anderson TJ, Condie A, Prosser J, Chetty U, Carter DC, et al. p53 allele losses, mutations and expressions in breast cancer and their relationship to clinic-pathological parameters. Int J Cancer 1992;50(4):528-32
  • 7. Oji Y, Ogawa H, Tamaki H, Oka Y, Tsuboi A, Kim EH, et al
  • Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res 1999;90(2):194-204
  • 8. Amin KM, Litzky LA, Smythe WR, Mooney AM, Morris JM, Mews DJ, et al. Wilms’ tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma
  • Am J Pathol 1995;146(2):344-56
  • 9. Kumar-Singh S, Segers K, Rodeck U, Backhovens H, Bogers J, Weyler J, et al. WT1 mutation in malignant mesothelioma and WT1 immunoreactivity in relation to p53 and growth factor receptor expression, cell-type transition, and prognosis. J Pathol 1997;181(1):67-74
  • 10. Menssen HD, Renkl HJ, Rodeck U, Kari C, Schwartz S, Thiel E. Detection of monoclonal antibodies of the Wilms’ tumor (WT1) nuclear protein in patients with acute leukemia. Int J Cancer 1997;70(5):518-23
  • 11. Haber DA, Englert C, Maheswaran S. Functional propeties of WT1. Med Pediatr Oncol 1996;27(5):453-5
  • 12. Tsuboi A, Oka Y, Osaki T, Kumagai T, Tachibana I, Hayashi S, et al. WT1 peptide-based immunotherapy for patients with lung cancer: report of two cases. Microbiol Immunol 2004;48(3):175-84
  • 13. Oji Y, Miyoshi Y, Koga S, Nakano Y, Ando A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in primary thyroid cancer. Cancer Sci 2003;94(7):606-11
  • 14. Oji Y, Inohara H, Nakazawa M, Nakano Y, Akahani S, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in head and neck squamous cell carcinoma. Cancer Sci 2003;94(6):523-9
  • 15. Oji Y, Yamamoto H, Nomura M, Nakano Y, Ikeba A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in colorectal adenocarcinoma. Cancer Sci 2003;94(8):712-7
  • 16. Benjamin LE, Fredericks WJ, Barr FG, Rauscher FJ 3rd. Fusion of the EWS1 and WT1 genes as a result of the t(11;22)(p13;q12) translocation in desmoplastic small round cell tumors. Med Pediatr Oncol 1996;27(5):434-9
  • 17. Netinatsunthorn W, Hanprasertpong J, Dechsukhum C, Leetanaporn R, Geater A. WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study. BMC Cancer. 2006;6:90
  • 18. Tajinda K, Carrol J, Roberts CR Jr. Regulation of insulin-like growth factor I receptor promoter activity by wild-type and mutant version of the WT1 tumor suppressor. Endocrinology 1999;140(10):4713-24
  • 19. Cooper MG. Tumor suppressor genes. The Cell:A Molecular Approach, 1st edn, ASM press, 1997:626-7
  • 20. Maheswaran S, Park S, Bernard A, Morris JF, Rauscher FJ 3d, Hill DE, et al. Physical and functional interaction between WT1 and p53 proteins. Proc Natl Acad Sci USA 1993; 90(11):5100-4
  • 21. Reizner N, Maor S, Sarfstein R, Abramovitch S, Welshons WV, Curran EM, et al. The WT1 Wilms' tumor suppressor gene product interacts with estrogen receptor-alpha and regulates IGF-I receptor gene transcription in breast cancer cells. J Mol Endocrinol 2005;35(1):135-44
  • 22. Tuna M, Chavez-Reyes A, Tari AM. HER2/neu increases the expression of Wilms' Tumor 1 (WT1) protein to stimulate Sphase proliferation and inhibit apoptosis in breast cancer cells
  • Oncogene 2005;24(9):1648-52
  • 23. Miyoshi Y, Ando A, Egawa C, Taguchi T, Tamaki Y, Tamaki H, et al. High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients. Clin Cancer Res 2002;8(5):1167-71
  • 24. Renshaw J, Orr RM, Walton MI, Te Poele R, Williams RD, Wancewicz EV, et al. Disruption of WT1 gene expression and exon 5 splicing following cytotoxic drug treatment: antisense down-regulation of exon 5 alters target gene expression and inhibits cell survival. Mol Cancer Ther 2004;3(11):1467-84
  • 25. Zapata-Benavides P, Tuna M, Lopez-Berestein G, Tari AM
  • Downregulation of Wilms' tumor 1 protein inhibits breast cancer proliferation. Biochem Biophys Res Commun 2002;295(4):784-90
  • 26. Oji Y, Miyoshi Y, Kiyotoh E, Koga S, Nakano Y, Ando A, et al
  • Absence of mutations in the Wilms' tumor gene WT1 in primary breast cancer. Jpn J Clin Oncol 2004;34(2):74-7
  • 27. Oka Y, Tsuboi A, Taguchi T, Osaki T, Kyo T, Nakajima H, et al. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci USA 2004;101(38):13885-90
  • 28. Morita S, Oka Y, Tsuboi A, Kawakami M, Maruno M, Izumoto S, et al. A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data. Jpn J Clin Oncol 2006;36(4):231-6
  • 29. Loeb DM, Evron E, Patel CB, Sharma PM, Niranjan B, Buluwela L, et al. Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. Cancer Res 2001;61(3):921-5
  • 30. Silberstein GB, Van Horn K, Strickland P, Roberts CT Jr, Daniel CW. Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer. Proc Natl Acad Sci USA 1997;94(15):8132-7.

Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer

Year 2011, Volume: 17 Issue: 2, 67 - 72, 01.03.2011

Abstract

Meme kanseri tüm dünyada kadınlarda görülen en sık kanser tipidir. Aynı klinikopatolojik evredeki kadınlarda meme kanserinin klinik seyri farklı olabilir, bu yüzden araştırmacılar tümör davranışını tahmin edebilmek için ek prognostik parametrelere odaklanmışlardır. Bu çalışmanın amacı, meme kanseri hastalarında tümör dokusunda Wilms Tumor 1 (WT1) ekspresyonunun prognostik önemi ve bunun bilinen prognostik değişkenlerle karşılaştırılmasıdır. Meme kanserli hastalarda, tümor ve tümör dokusu çevresindeki dokularda WT1 protein ekspresyonu ile prognostik faktörlerden yaş, patolojik tip, aksiller lenf nodu tutulumu, östrojen reseptör (ER) durumu, menopoz durumu, evre (TNM), tümör gradı ve tedavi arasındaki ilişki araştırıldı. WT1 monoklonal antikor (mAb) ile premenopozal durum arasında orta derecede bir ilişki saptandı (p=0.051). Ek olarak, tümör çevresindeki doku ile tümör gradı (p=0.045), evre (p=0.026), lenf nodu (p=0.026) ve aksiller tutulum (p=0.02) arasında anlamlı ilişki saptandı. Nükssüz sağkalım, nüks bölgeleri ile tümör dokusu ve tümör çevresi dokudaki WT1 mAb arasında anlamlı ilişki gözlenmedi (p=0.36). İnsan meme kanseri dokularında WT1 mAb gösterilmiştir ve bu çalışmada parafindeki doku örneklerine karşı monoklonal antikorlar kullanıldı. Bu sonuçlar premenopozal dönemde tümör dokusunda WT1 ekspresyonunun postmenopozal döneme göre daha fazla olduğunu göstermektedir. Bu sonuçların teyid edilmesi için meme kanserinde WT1 ekspresyonu için daha büyük çalışmalara ihtiyaç vardır.

References

  • 1. Gillmore R, Xue SA, Holler A, Kaeda J, Hadjiminas D, Healy V, et al. Detection of Wilms' tumor antigen--specific CTL in tumor-draining lymph nodes of patients with early breast cancer. Clin Cancer Res 2006;12(1):34-42
  • 2. Fisher B, Osborne CK, Margolese RG, Bloomer WD. Neoplasm of the breast. In: Holland JF, Bast RC Jr, Morton DL, Frei E III, Kufe DW, Weichselbaum RR (eds). Cancer Medicine,Williams and Wilkins Co: International Edition, 1997: 2362-6
  • 3. Hennessy C, Henry JA, May FE, Westley BR, Angus B, Lennard TW. Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. J Natl Cancer Inst 1991;83(4):281-5
  • 4. Nemoto T, Natarajan N, Bedwani R, Vana J, Murphy GP
  • Breast cancer in the medial half. Results of the 1978 national survey of the American College of Surgeons. Cancer 1983;51(8):1333-8
  • 5. Sauer T, Furu I, Beraki K, Jebsen PW, Ormerod E, Naess O
  • nm23 protein expression in fine needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status and ploidy. Cancer 1998;84(2):109-14
  • 6. Thompson AM, Anderson TJ, Condie A, Prosser J, Chetty U, Carter DC, et al. p53 allele losses, mutations and expressions in breast cancer and their relationship to clinic-pathological parameters. Int J Cancer 1992;50(4):528-32
  • 7. Oji Y, Ogawa H, Tamaki H, Oka Y, Tsuboi A, Kim EH, et al
  • Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res 1999;90(2):194-204
  • 8. Amin KM, Litzky LA, Smythe WR, Mooney AM, Morris JM, Mews DJ, et al. Wilms’ tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma
  • Am J Pathol 1995;146(2):344-56
  • 9. Kumar-Singh S, Segers K, Rodeck U, Backhovens H, Bogers J, Weyler J, et al. WT1 mutation in malignant mesothelioma and WT1 immunoreactivity in relation to p53 and growth factor receptor expression, cell-type transition, and prognosis. J Pathol 1997;181(1):67-74
  • 10. Menssen HD, Renkl HJ, Rodeck U, Kari C, Schwartz S, Thiel E. Detection of monoclonal antibodies of the Wilms’ tumor (WT1) nuclear protein in patients with acute leukemia. Int J Cancer 1997;70(5):518-23
  • 11. Haber DA, Englert C, Maheswaran S. Functional propeties of WT1. Med Pediatr Oncol 1996;27(5):453-5
  • 12. Tsuboi A, Oka Y, Osaki T, Kumagai T, Tachibana I, Hayashi S, et al. WT1 peptide-based immunotherapy for patients with lung cancer: report of two cases. Microbiol Immunol 2004;48(3):175-84
  • 13. Oji Y, Miyoshi Y, Koga S, Nakano Y, Ando A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in primary thyroid cancer. Cancer Sci 2003;94(7):606-11
  • 14. Oji Y, Inohara H, Nakazawa M, Nakano Y, Akahani S, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in head and neck squamous cell carcinoma. Cancer Sci 2003;94(6):523-9
  • 15. Oji Y, Yamamoto H, Nomura M, Nakano Y, Ikeba A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in colorectal adenocarcinoma. Cancer Sci 2003;94(8):712-7
  • 16. Benjamin LE, Fredericks WJ, Barr FG, Rauscher FJ 3rd. Fusion of the EWS1 and WT1 genes as a result of the t(11;22)(p13;q12) translocation in desmoplastic small round cell tumors. Med Pediatr Oncol 1996;27(5):434-9
  • 17. Netinatsunthorn W, Hanprasertpong J, Dechsukhum C, Leetanaporn R, Geater A. WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study. BMC Cancer. 2006;6:90
  • 18. Tajinda K, Carrol J, Roberts CR Jr. Regulation of insulin-like growth factor I receptor promoter activity by wild-type and mutant version of the WT1 tumor suppressor. Endocrinology 1999;140(10):4713-24
  • 19. Cooper MG. Tumor suppressor genes. The Cell:A Molecular Approach, 1st edn, ASM press, 1997:626-7
  • 20. Maheswaran S, Park S, Bernard A, Morris JF, Rauscher FJ 3d, Hill DE, et al. Physical and functional interaction between WT1 and p53 proteins. Proc Natl Acad Sci USA 1993; 90(11):5100-4
  • 21. Reizner N, Maor S, Sarfstein R, Abramovitch S, Welshons WV, Curran EM, et al. The WT1 Wilms' tumor suppressor gene product interacts with estrogen receptor-alpha and regulates IGF-I receptor gene transcription in breast cancer cells. J Mol Endocrinol 2005;35(1):135-44
  • 22. Tuna M, Chavez-Reyes A, Tari AM. HER2/neu increases the expression of Wilms' Tumor 1 (WT1) protein to stimulate Sphase proliferation and inhibit apoptosis in breast cancer cells
  • Oncogene 2005;24(9):1648-52
  • 23. Miyoshi Y, Ando A, Egawa C, Taguchi T, Tamaki Y, Tamaki H, et al. High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients. Clin Cancer Res 2002;8(5):1167-71
  • 24. Renshaw J, Orr RM, Walton MI, Te Poele R, Williams RD, Wancewicz EV, et al. Disruption of WT1 gene expression and exon 5 splicing following cytotoxic drug treatment: antisense down-regulation of exon 5 alters target gene expression and inhibits cell survival. Mol Cancer Ther 2004;3(11):1467-84
  • 25. Zapata-Benavides P, Tuna M, Lopez-Berestein G, Tari AM
  • Downregulation of Wilms' tumor 1 protein inhibits breast cancer proliferation. Biochem Biophys Res Commun 2002;295(4):784-90
  • 26. Oji Y, Miyoshi Y, Kiyotoh E, Koga S, Nakano Y, Ando A, et al
  • Absence of mutations in the Wilms' tumor gene WT1 in primary breast cancer. Jpn J Clin Oncol 2004;34(2):74-7
  • 27. Oka Y, Tsuboi A, Taguchi T, Osaki T, Kyo T, Nakajima H, et al. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci USA 2004;101(38):13885-90
  • 28. Morita S, Oka Y, Tsuboi A, Kawakami M, Maruno M, Izumoto S, et al. A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data. Jpn J Clin Oncol 2006;36(4):231-6
  • 29. Loeb DM, Evron E, Patel CB, Sharma PM, Niranjan B, Buluwela L, et al. Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. Cancer Res 2001;61(3):921-5
  • 30. Silberstein GB, Van Horn K, Strickland P, Roberts CT Jr, Daniel CW. Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer. Proc Natl Acad Sci USA 1997;94(15):8132-7.
There are 37 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Celaletdin Camcı This is me

Mehmet Emin Kalender This is me

Semra Paydaş This is me

Alper Sevinç This is me

Suzan Zorludemir This is me

Ali Suner This is me

Publication Date March 1, 2011
Published in Issue Year 2011 Volume: 17 Issue: 2

Cite

APA Camcı, C., Kalender, M. E., Paydaş, S., Sevinç, A., et al. (2011). Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer. Gaziantep Medical Journal, 17(2), 67-72.
AMA Camcı C, Kalender ME, Paydaş S, Sevinç A, Zorludemir S, Suner A. Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer. Gaziantep Medical Journal. March 2011;17(2):67-72.
Chicago Camcı, Celaletdin, Mehmet Emin Kalender, Semra Paydaş, Alper Sevinç, Suzan Zorludemir, and Ali Suner. “Prognostic Significance of Wilms Tumor 1 (WT1) Protein Expression in Breast Cancer”. Gaziantep Medical Journal 17, no. 2 (March 2011): 67-72.
EndNote Camcı C, Kalender ME, Paydaş S, Sevinç A, Zorludemir S, Suner A (March 1, 2011) Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer. Gaziantep Medical Journal 17 2 67–72.
IEEE C. Camcı, M. E. Kalender, S. Paydaş, A. Sevinç, S. Zorludemir, and A. Suner, “Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer”, Gaziantep Medical Journal, vol. 17, no. 2, pp. 67–72, 2011.
ISNAD Camcı, Celaletdin et al. “Prognostic Significance of Wilms Tumor 1 (WT1) Protein Expression in Breast Cancer”. Gaziantep Medical Journal 17/2 (March 2011), 67-72.
JAMA Camcı C, Kalender ME, Paydaş S, Sevinç A, Zorludemir S, Suner A. Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer. Gaziantep Medical Journal. 2011;17:67–72.
MLA Camcı, Celaletdin et al. “Prognostic Significance of Wilms Tumor 1 (WT1) Protein Expression in Breast Cancer”. Gaziantep Medical Journal, vol. 17, no. 2, 2011, pp. 67-72.
Vancouver Camcı C, Kalender ME, Paydaş S, Sevinç A, Zorludemir S, Suner A. Prognostic significance of Wilms Tumor 1 (WT1) protein expression in breast cancer. Gaziantep Medical Journal. 2011;17(2):67-72.