Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Relationships Between C-Kit Expression and Mean Platelet Volume in Benign, Preneoplastic and Neoplastic Endometrium

  • Sehitoglu, Ibrahim (Department of Pathology, Faculty of Medicine, Recep Tayyip Erdogan University) ;
  • Bedir, Recep (Department of Pathology, Faculty of Medicine, Recep Tayyip Erdogan University) ;
  • Ural, Ulku Mete (Department of Obstetrics and Gynecology, Faculty of Medicine, Recep Tayyip Erdogan University) ;
  • Gucer, Hasan (Department of Pathology, Faculty of Medicine, Recep Tayyip Erdogan University) ;
  • Yurdakul, Cuneyt (Department of Pathology, Rize Training and Research Hospital) ;
  • Cure, Medine Cumhur (Department of Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University) ;
  • Cure, Erkan (Department of Internal Medicine, Faculty of Medicine, Recep Tayyip Erdogan University) ;
  • Yuce, Suleyman (Internal Medicine, Kumru State Hospital) ;
  • Sahin, Figen Kir (Department of Obstetrics and Gynecology, Faculty of Medicine, Recep Tayyip Erdogan University)
  • Published : 2015.03.09
Download PDF
⟨ Previous Next ⟩

Abstract

Background: c-Kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker for demonstrating thrombocyte function. We aimed to investigate whether c-kit is expressed in benign, preneoplastic and neoplastic endometrial tissues and whether MPV has a relation with c-kit expression and its intensity. Materials and Methods: c-Kit expression was investigated immunohistochemically in 10 samples of normal endometrium (n=10), simple endometrial hyperplasia (5 cases with atypia and 10 cases without atypia), complex endometrial hyperplasia (10 cases with atypia and 10 cases without atypia) and endometrial cancer (EC) (10 cases grade I and 10 cases grade II) and MPV of all cases was checked. Results: c-Kit expression was observed at very low rates in cases with normal endometrial tissues (NE) and in hyperplasia without atypia. c-Kit expression and immunostaining were strong in endometrial atypia and EC. MPV levels of complex atypical endometrial hyperplasia (CAEH) (p:0.002), EC grade I (ECG I) (p<0.001) and EC grade II (ECG II) (p<0.001) were significantly elevated when compared with the NE group. Both c-kit expression and intensity of immunostaining had a positive correlation with MPV level. Conclusions: While c-kit expression and intensity of immunostaining were mildly positive in NE and hyperplasia without atypia, they were clearly observed in EC and hyperplasia with atypia. As c-kit expression is related to the mutagenesis a long-term followup may be needed in these cases. A high MPV level may be a good test for demonstrating c-kit expression and intensity of immunostaining.

Keywords

References

  1. Afsar CU, Gunaldi M, Kum P, et al (2014). Pancreatic carcinoma, thrombosis and mean platelet volume: single center experience from the southeast region of Turkey. Asian Pac J Cancer Prev, 15, 9143-6. https://doi.org/10.7314/APJCP.2014.15.21.9143
  2. Andreadis D, Epivatianos A, Poulopoulos A et al (2006). Detection of C-KIT (CD117) molecule in benign and malignant salivary gland tumours. Oral Oncol, 42, 57-65.
  3. Cumhur Cure M, Cure E, Yuce S, Yazici T, Karakoyun I, Efe H (2014). Mean platelet volume and vitamin D level. Ann Lab Med, 34, 98-103. https://doi.org/10.3343/alm.2014.34.2.98
  4. d'Auriol L, Mattei MG, Andre C, Galibert F (1988). Localization of the human c-kit protooncogene on the q11-q12 region of chromosome 4. Hum Genet, 78, 374-6. https://doi.org/10.1007/BF00291740
  5. Ding J, Li XM, Liu SL, Zhang Y, Li T (2014). Overexpression of platelet-derived growth factor-D as a poor prognosticator in endometrial cancer. Asian Pac J Cancer Prev, 15, 3741-5. https://doi.org/10.7314/APJCP.2014.15.8.3741
  6. Dossus L, Lukanova A, Rinaldi S et al (2013). Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis. Am J Epidemiol, 177, 787-99. https://doi.org/10.1093/aje/kws309
  7. Elmore LW, Domson K, Moore JR, Kornstein M, Burks RT (2001). Expression of c-kit (CD117) in benign and malignant human endometrial epithelium. Arch Pathol Lab Med, 125, 146-51.
  8. Jansson S, Bendahl PO, Grabau DA et al (2014). The three receptor tyrosine kinases c-KIT, VEGFR2 and PDGFR${\alpha}$, closely spaced at 4q12, show increased protein expression in triple-negative breast cancer. PLoS One, 9, 102176. https://doi.org/10.1371/journal.pone.0102176
  9. Inoue M, Kyo S, Fujita M, Enomoto T, Kondoh G (1994). Coexpression of the c-kit receptor and the stem cell factor in gynecological tumors. Cancer Res, 54, 3049-53.
  10. Lammie A, Drobnjak M, Gerald W, Saad A, Cote R, Cordon-Cardo C (1994). Expression of c-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem, 42, 1417-25. https://doi.org/10.1177/42.11.7523489
  11. Linkov F, Edwards R, Balk J et al (2008). Endometrial hyperplasia, endometrial cancer and prevention: gaps in existing research of modifiable risk factors. Eur J Cancer, 44, 1632-44. https://doi.org/10.1016/j.ejca.2008.05.001
  12. Matowicka-Karna J, Kamocki Z, Polinska B, Osada J, Kemona H (2013). Platelets and inflammatory markers in patients with gastric cancer. Clin Dev Immunol, 2013, 401623.
  13. Menczer J, Kravtsov V, Levy T, et al (2005). Expression of c-kit in uterine carcinosarcoma. Gynecol Oncol, 96, 210-5. https://doi.org/10.1016/j.ygyno.2004.09.045
  14. Miettinen M, Lasota J (2005). KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol, 13, 205-20. https://doi.org/10.1097/01.pai.0000173054.83414.22
  15. Natali PG, Berlingieri MT, Nicotra MR et al (1995). Transformation of thyroid epithelium is associated with loss of c-kit receptor. Cancer Res, 55, 1787-91.
  16. Natali PG, Nicotra MR, Sures I, Santoro E, Bigotti A, Ullrich A (1992). Expression of c-kit receptor in normal and transformed human nonlymphoid tissues. Cancer Res, 52, 6139-43.
  17. Oge T, Yalcin OT, Ozalp SS, Isikci T (2013). Platelet volume as a parameter for platelet activation in patients with endometrial cancer. J Obstet Gynaecol, 33, 301-4. https://doi.org/10.3109/01443615.2012.758089
  18. Park Y, Schoene N, Harris W (2002). Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets, 13, 301-6. https://doi.org/10.1080/095371002220148332
  19. Salomonsson A, Jonsson M, Isaksson S et al (2013). Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma. Genes Chromosomes Cancer, 52, 1088-96. https://doi.org/10.1002/gcc.22103
  20. Scobie JV, Acs G, Bandera CA et al (2003). C-kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance. Int J Gynecol Pathol, 22, 149-55. https://doi.org/10.1097/00004347-200304000-00006
  21. Terada T (2012). Protein expression and gene mutation status of KIT and PDGFRA in renal cell carcinoma. Histol Histopathol, 27, 297-302.
  22. Trinh DT, Shibata K, Hirosawa T et al (2012). Diagnostic utility of CD117, CD133, SALL4, OCT4, TCL1 and glypican-3 in malignant germ cell tumors of the ovary. J Obstet Gynaecol Res, 38, 841-8. https://doi.org/10.1111/j.1447-0756.2011.01798.x
  23. Varol E, Ozaydin M (2014). Confounding factors should be considered in mean platelet volume evaluation in endometrial cancer. J Obstet Gynaecol, 34, 455. https://doi.org/10.3109/01443615.2013.874985
  24. Wang Y, Qiu H, Hu W, Li S, Yu J (2014). Over-expression of platelet-derived growth factor-D promotes tumor growth and invasion in endometrial cancer. Int J Mol Sci, 15, 4780-94. https://doi.org/10.3390/ijms15034780
  25. Weigel MT, Ghazoui Z, Dunbier A, et al (2012). Preclinical and clinical studies of estrogen deprivation support the PDGF/Abl pathway as a novel therapeutic target for overcoming endocrine resistance in breast cancer. Breast Cancer Res, 14, 78. https://doi.org/10.1186/bcr3191
  26. Xiao H, Wang J, Liu Y, Li L (2014). Relative influence of c-Kit expression and epidermal growth factor receptor gene amplification on survival in patients with non-small cell lung cancer. Oncol Lett, 8, 582-8. https://doi.org/10.3892/ol.2014.2173
  27. Yarden Y, Kuang WJ, Yang-Feng T et al (1987). Human protooncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J, 6, 3341-51.
  28. Yilmaz E, Celik O, Simsek Y et al (2012). c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer. Arch Gynecol Obstet, 286, 197-200. https://doi.org/10.1007/s00404-012-2276-8
  29. Zhu Y, Wang Y, Guan B et al (2014). C-kit and PDGFRA gene mutations in triple negative breast cancer. Int J Clin Exp Pathol, 7, 4280-5.

Cited by

  1. Diagnostic and prognostic roles of the mean platelet volume in malignant tumors: a systematic review and meta-analysis vol.27, pp.8, 2016, https://doi.org/10.3109/09537104.2016.1169265