Araştırma Makalesi
BibTex RIS Kaynak Göster

Kolon Poliplerinde WT1 Ekspresyonunun İncelenmesi

Yıl 2018, Cilt: 23 Sayı: 2, 79 - 83, 19.05.2018
https://doi.org/10.21673/anadoluklin.364563

Öz

Amaç: WT1, ilk olarak Wilms tümörü gelişimini etkileyen tümör baskılayıcı bir gen olarak tespit edilmiş olsa da, kolon kanseri gibi bazı malignitelerde ekspresyonunun arttığı, dolayısıyla onkojenik özelliklerinin olduğu da bildirilmektedir. Bu çalışmanın amacı WT1 ekspresyonunun hastanın yaşına, cinsiyetine, örneğin alındığı bölgeye ve patolojik tanı türüne göre değişip değişmediğini tespit etmektir.

Gereç ve Yöntemler: Patoloji anabilim dalına gönderilmiş kolon polipli 32 hastaya ait parafin blokların ve patoloji raporlarının retrospektif histopatolojik değerlendirilmesi yapılmıştır. İstatistiksel olarak p<0,05 anlamlı kabul edilmiştir.

Bulgular: WT1 ekspresyonu ile hasta yaşı ortalaması, cinsiyet, lokalizasyon, çap, histopatolojik tanı parametreleri arasında istatistiksel olarak anlamlı ilişki izlenmedi (sırasıyla p=0,235; p=0,423; p=0,338; p=0,719; p=0,338). Bununla birlikte OR (odds ratio) değerleri dikkate alındığında ise klinik olarak anlamlı farklılıkların olduğu görüldü. Pozitif boyanma; adenomlarda (neoplastik grup) poliplere (non neoplastik grup) göre 4,308 kat (OR=4,308), transvers kolondan anüse kadar olan kısımda transvers kolona göre 4,308 kat (OR=4,308), ve kadınlarda erkeklere göre 2,333 kat (OR=2,333) daha yüksekti.

Tartışma ve  Sonuç: Çalışmamızın bulguları poliplerde WT1 ekspresyonu ile cinsiyet, tanı ve biyopsinin alındığı yer arasında istatistiksel olarak anlamlı ilişki olmadığını, fakat OR değerleri dikkate alındığında klinik olarak anlamlı farklılıkların olduğunu düşündürmektedir. Rutin immünohistokimyasal inceleme ile WT1 ekspresyonu olan benign ve prekanseröz poliplerin tespiti, kolon tümörleri bakımından yüksek risk altındaki bireylerde WT1 immünoterapisinin ve aşı etkinliğinin daha iyi anlaşılmasına katkıda bulunabilir. 

Kaynakça

  • 1. Hohenstein P., Hastie N.D. Themanyfacets of theWilms' tumour gene, WT1, Human Molecular Genetics, October 2006;Volume 15, Issue suppl-2, 15, pp.: 196-201.
  • 2. Colucci P.M., Yale S.H., Rall C.J.; Colorectal Polyps. Clinical Medicine and Research. 2003;1(3):261-262.
  • 3. Siegel R.L., Miller K.D., Jemal A.; Cancerstatistics, 2017; CA Cancer J Clin. 2017; 67:7-30.
  • 4. www.kanser.gov.tr [internet]. Türkiye Kanser İstatistikleri. Ankara, 2017; Erişim adresi: http://kanser.gov.tr/Dosya/ca_istatistik/2014-RAPOR._uzun.pdf 5. Yamaner S.Kolorektal Polipler; Kolon Rektum Hast. Derg. 2007;17:1-8.
  • 6. Ince A.T.,Ovunç O. Kolon Polipleri ve kromoendoskopisi. Güncel Gastroenteroloji Dergisi, 2003; 7/4: 255-265.
  • 7. Haber D.A., Buckler A.J., Glaser T., Call K.M., Pelletier J., Sohn R.L., et al. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell. 1990 Jun; 29;61(7):1257-69.
  • 8. www.tuik.gov.tr [internet]. Ölüm Nedeni İstatistikleri, 2016. 27 Nisan 2017; Sayı: 24572, Erişim adresi: http://www.tuik.gov.tr/PreHaberBultenleri.do?id=24572.
  • 9. Oji Y., Yano M., Nakano Y., Abeno S., Nakatsuka S., Ikeba A., et al. Overexpression of the Wilms’ Tumor Gene WT1 in Esophageal Cancer. Anticancer Research 2004; 24: 3103-3108.
  • 10. Yang L., Han Y., Suarez Saiz F. & Minden M.D. A tumor suppressor and oncogene: the WT1 story. Leukemia 2007; 21, 868–76.
  • 11. Sugiyama H. WT1 (Wilms' tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol 2010; 40, 377–87.
  • 12. Stoner G.D., Gupta A.: Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis 2001; 22: 1737-1746.
  • 13. Niksic M., Slight J., Sanford J.R., Caceres J.F., Hastie N.D. The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Genet 2004;13: 463-471.
  • 14. Tatsumi N., Oji Y., Tsuji N., Tsuda A., Higashio M., Aoyagi S. et al. Wilms' tumor gene WT1-shRNA as a potent apoptosis-inducing agent for solid tumors. Int J Oncol 2008; 32, 701-11.
  • 15. Hartkamp J., Carpenter B. & Roberts S. G. The Wilms' tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi. Mol Cell 2010; 37, 159–71.
  • 16. Wu C., Zhu W., Qian J., He S., Wu C., Chen Y., et al. WT1 Promotes Invasion of NSCLC via Suppression of CDH1. J Thorac Oncol 2013; 8, 1163-9.
  • 17. Vicent S., Chen R., Sayles L.C., Lin C., Walker R.G., Gillespie A.K., et al. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest 2010; 120, 3940–52.
  • 18. Brett A., Pandey S. & Fraizer G. The Wilms' tumor gene (WT1) regulates E-cadherin expression and migration of prostate cancer cells. Mol Cancer 2013; 12, 3.
  • 19. McCarty G., Awad O. & Loeb D.M. WT1 protein directly regulates expression of vascular endothelial growth factor and is a mediator of tumor response to hypoxia. J Biol Chem 2011; 286, 43634–43.
  • 20. Han Y., Yang L., Suarez-Saiz F., San-Marina S., Cui J., Minden M.D. Wilms' tumor 1 suppressor gene mediates antiestrogen resistance via down-regulation of estrogen receptor-alpha expression in breast cancer cells. Mol Cancer Res 2008; 6, 1347-55.
  • 21. Wu F., Yuan G., Chen J., Wang C. Network analysis based on TCGA reveals hub genes in colon cancer.Contemp Oncol (Pozn). 2017; 21(2):136-144.
  • 22. Kim M.K.H., McGarry T.J., Broin P.O., Flatow J.M., Golden A.A., Licht J.D. An integrated genome screen identifies the Wnt signaling pathway as a major target of WT1. Proc Natl Acad Sci USA 2009;106:11154-9.
  • 23. Pohl J. Hyperplastic Polyposis Syndrome. Video Journal and Encyclopedia of GI Endoscopy. 2013; 1 (2): 370–371.

An Investigation of WT1 Expression in Colon Polyps

Yıl 2018, Cilt: 23 Sayı: 2, 79 - 83, 19.05.2018
https://doi.org/10.21673/anadoluklin.364563

Öz

Aim: Although WT1 was first identified as a tumor suppressor gene affecting Wilms’ tumor development, it has also been reported that its expression increases in certain malignancies such as colon cancer, and that it therefore has oncogenic properties. In this study, we aimed to determine dependence of WT1 expression on patient age and sex, type of pathological diagnosis, and the sample-taking area.

Materials and Methods: Paraffin-embedded blocks and pathology reports of 32 patients with colon polyps that had been sent to pathology department were histopathologically reviewed retrospectively. p<0.05 was considered statistically significant.

Results: No statistically significant relationship was observed between WT1 expression and the parameters of mean patient age, sex, localization, diameter, and histopathological diagnosis (p=0.235, p=0.423, p=0.338, p=0.719, p=0.338, respectively). However, when OR (odds ratio) values were considered, it was thought that there were clinically significant differences. Positive staining was 4.308 times higher in adenomas (neoplastic group) than in polyps (nonneoplastic group) (OR=4.308), 4,308 times higher in the portion from the transverse colon to the anus than in the transverse colon (OR=4.308), and 2.333 times higher in women than in men (OR=2.333).

Discussion and Conclusion: The study findings suggest that there is no statistically significant relationship between presence of WT1 expression in polyps and sex, diagnosis, and sample-taking area, but that there is clinically significant differences when OR values are considered. Detection of benign and precancerous polyps with WT1 expression through routine immunohistochemical examination could contribute to better understanding WT1 immunotherapy and vaccine efficacy in individuals at high risk of developing colonic tumors. 

Kaynakça

  • 1. Hohenstein P., Hastie N.D. Themanyfacets of theWilms' tumour gene, WT1, Human Molecular Genetics, October 2006;Volume 15, Issue suppl-2, 15, pp.: 196-201.
  • 2. Colucci P.M., Yale S.H., Rall C.J.; Colorectal Polyps. Clinical Medicine and Research. 2003;1(3):261-262.
  • 3. Siegel R.L., Miller K.D., Jemal A.; Cancerstatistics, 2017; CA Cancer J Clin. 2017; 67:7-30.
  • 4. www.kanser.gov.tr [internet]. Türkiye Kanser İstatistikleri. Ankara, 2017; Erişim adresi: http://kanser.gov.tr/Dosya/ca_istatistik/2014-RAPOR._uzun.pdf 5. Yamaner S.Kolorektal Polipler; Kolon Rektum Hast. Derg. 2007;17:1-8.
  • 6. Ince A.T.,Ovunç O. Kolon Polipleri ve kromoendoskopisi. Güncel Gastroenteroloji Dergisi, 2003; 7/4: 255-265.
  • 7. Haber D.A., Buckler A.J., Glaser T., Call K.M., Pelletier J., Sohn R.L., et al. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell. 1990 Jun; 29;61(7):1257-69.
  • 8. www.tuik.gov.tr [internet]. Ölüm Nedeni İstatistikleri, 2016. 27 Nisan 2017; Sayı: 24572, Erişim adresi: http://www.tuik.gov.tr/PreHaberBultenleri.do?id=24572.
  • 9. Oji Y., Yano M., Nakano Y., Abeno S., Nakatsuka S., Ikeba A., et al. Overexpression of the Wilms’ Tumor Gene WT1 in Esophageal Cancer. Anticancer Research 2004; 24: 3103-3108.
  • 10. Yang L., Han Y., Suarez Saiz F. & Minden M.D. A tumor suppressor and oncogene: the WT1 story. Leukemia 2007; 21, 868–76.
  • 11. Sugiyama H. WT1 (Wilms' tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol 2010; 40, 377–87.
  • 12. Stoner G.D., Gupta A.: Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis 2001; 22: 1737-1746.
  • 13. Niksic M., Slight J., Sanford J.R., Caceres J.F., Hastie N.D. The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Genet 2004;13: 463-471.
  • 14. Tatsumi N., Oji Y., Tsuji N., Tsuda A., Higashio M., Aoyagi S. et al. Wilms' tumor gene WT1-shRNA as a potent apoptosis-inducing agent for solid tumors. Int J Oncol 2008; 32, 701-11.
  • 15. Hartkamp J., Carpenter B. & Roberts S. G. The Wilms' tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi. Mol Cell 2010; 37, 159–71.
  • 16. Wu C., Zhu W., Qian J., He S., Wu C., Chen Y., et al. WT1 Promotes Invasion of NSCLC via Suppression of CDH1. J Thorac Oncol 2013; 8, 1163-9.
  • 17. Vicent S., Chen R., Sayles L.C., Lin C., Walker R.G., Gillespie A.K., et al. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest 2010; 120, 3940–52.
  • 18. Brett A., Pandey S. & Fraizer G. The Wilms' tumor gene (WT1) regulates E-cadherin expression and migration of prostate cancer cells. Mol Cancer 2013; 12, 3.
  • 19. McCarty G., Awad O. & Loeb D.M. WT1 protein directly regulates expression of vascular endothelial growth factor and is a mediator of tumor response to hypoxia. J Biol Chem 2011; 286, 43634–43.
  • 20. Han Y., Yang L., Suarez-Saiz F., San-Marina S., Cui J., Minden M.D. Wilms' tumor 1 suppressor gene mediates antiestrogen resistance via down-regulation of estrogen receptor-alpha expression in breast cancer cells. Mol Cancer Res 2008; 6, 1347-55.
  • 21. Wu F., Yuan G., Chen J., Wang C. Network analysis based on TCGA reveals hub genes in colon cancer.Contemp Oncol (Pozn). 2017; 21(2):136-144.
  • 22. Kim M.K.H., McGarry T.J., Broin P.O., Flatow J.M., Golden A.A., Licht J.D. An integrated genome screen identifies the Wnt signaling pathway as a major target of WT1. Proc Natl Acad Sci USA 2009;106:11154-9.
  • 23. Pohl J. Hyperplastic Polyposis Syndrome. Video Journal and Encyclopedia of GI Endoscopy. 2013; 1 (2): 370–371.
Toplam 22 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm ORJİNAL MAKALE
Yazarlar

Ali Aslan 0000-0002-9674-5618

Havva Erdem

Mürüvvet Akçay Çelik

Arzu Şahin

Soner Çankaya

Yayımlanma Tarihi 19 Mayıs 2018
Kabul Tarihi 4 Mart 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 23 Sayı: 2

Kaynak Göster

Vancouver Aslan A, Erdem H, Akçay Çelik M, Şahin A, Çankaya S. Kolon Poliplerinde WT1 Ekspresyonunun İncelenmesi. Anadolu Klin. 2018;23(2):79-83.

13151 This Journal licensed under a CC BY-NC (Creative Commons Attribution-NonCommercial 4.0) International License.