Asian Pacific Journal of Cancer Prevention

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

DOI QR Code

Prognostic Impact of Cyclin D1, Cyclin E and P53 on Gastroenteropancreatic Neuroendocrine Tumours

  • Liu, Shu-Zheng (Department of Epidemiology, College of Public Health of Zhengzhou University) ;
  • Zhang, Fang (The Human Resource Department, the First Affiliated Hospital of Henan University of TCM) ;
  • Chang, Yu-Xi (Department of Pathology, the Tumor Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital) ;
  • Ma, Jie (Department of Pathology, the Tumor Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital) ;
  • Li, Xu (Department of Pathology, the Tumor Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital) ;
  • Li, Xiao-Hong (Department of Pathology, the Tumor Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital) ;
  • Fan, Jin-Hu (Department of Cancer Epidemiology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences) ;
  • Duan, Guang-Cai (Department of Epidemiology, College of Public Health of Zhengzhou University) ;
  • Sun, Xi-Bin (Henan Cancer Research and Control Office, Henan Cancer Hospital)
  • Published : 2013.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP-NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (${\geq}$ 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (${\geq}$ 10% positive nuclei) in 33 (49%). High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.

Keywords

References

  1. Ahn MJ, Kim BH, Sohn JH, et al (1998). Expression of Cyclin D1 and Cyclin E in human gastric carcinoma and its clinicopathologic significance. J Korean Med Sci, 13, 513-18. https://doi.org/10.3346/jkms.1998.13.5.513
  2. Bosman F, Carneiro F (2010). WHO classification of tumours, pathology and genetics otumours of the digestive system. Lyon, IARC Press.
  3. Cho MY, Kim JM, Sohn JH, et al (2012). Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study. Cancer Res Treat, 44, 157-65. https://doi.org/10.4143/crt.2012.44.3.157
  4. Corin I, Larsson L, Bergstrom J, et al (2010). A study of the expression of Cyclin E and its isoforms in tumor and adjacent mucosa, correlated to patient outcome in early colon cancer. Acta Oncol, 49, 63-9. https://doi.org/10.3109/02841860903268049
  5. Florenes VA, Faye RS, Maelandsmo GM, et al (2000). Levels of Cyclin D1 and D3 in malignant melanoma: deregulated Cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res, 6, 3614-20.
  6. Grabowski P, Schrader J, Wagner J, et al (2008). Loss of nuclear p27 expression and its prognostic role in relation to Cyclin E and p53 mutation in gastroenteropancreatic neuroendocrine tumors. Clin Cancer Res, 14, 7378-84. https://doi.org/10.1158/1078-0432.CCR-08-0698
  7. Heah KG, Hassan MI, Huat SC (2011). p53 Expression as a marker of microinvasion in oral squamous cell carcinoma. Asian Pac J Cancer Prev, 12, 1017-22.
  8. Hemminki K, Li X (2001). Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer, 92, 2204-10. https://doi.org/10.1002/1097-0142(20011015)92:8<2204::AID-CNCR1564>3.0.CO;2-R
  9. Ioachim E. (2008). Expression patterns of Cyclins D1, E and Cyclin-dependent kinase inhibitors p21waf1/cip1, p27kip1 in colorectal carcinoma: correlation with other cell cycle regulators (pRb, p53 and Ki-67 and PCNA) and clinicopathological features. Int J Clin Pract, 62, 1736-43. https://doi.org/10.1111/j.1742-1241.2006.01105.x
  10. Kamai T, Takagi K, Asami H, et al (2001). Decreasing of p27(Kip1)and Cyclin E protein levels is associated with progression from superficial into invasive bladder cancer. Br J Cancer, 84, 1242-51. https://doi.org/10.1054/bjoc.2000.1736
  11. Kawahara M, Kammori M, Kanauchi H, et al (2002). Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumours. Eur J Surg Oncol, 28, 140-46. https://doi.org/10.1053/ejso.2001.1229
  12. Kishimoto I, Mitomi H, Ohkura Y, et al (2008). Abnormal expression of p16(INK4a), Cyclin D1, Cyclin-dependent kinase 4 and retinoblastoma protein in gastric carcinomas. J Surg Oncol, 98, 60-6. https://doi.org/10.1002/jso.21087
  13. Lepage C, Bouvier AM, Phelip JM, et al (2004). Incidence and management of malignant digestive endocrine tumours in a well defined French population. Gut, 53, 549-53. https://doi.org/10.1136/gut.2003.026401
  14. Modlin IM, Lye KD, Kidd M (2003). A 5-decade analysis of 13,715 carcinoid tumors. Cancer, 97, 934-59. https://doi.org/10.1002/cncr.11105
  15. Quaedvlieg PF, Visser O, Lamers CB, et al (2001). Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol, 12, 1295-300. https://doi.org/10.1023/A:1012272314550
  16. Richter J, Wagner U, Kononen J, et al (2000). High-throughput tissue microarray analysis of Cyclin E gene amplification and overexpression in urinary bladder cancer. Am J Pathol, 157, 787-94. https://doi.org/10.1016/S0002-9440(10)64592-0
  17. Rorstad O (2005). Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol, 89, 151-60. https://doi.org/10.1002/jso.20179
  18. Sakaguchi T, Watanabe A, Sawada H, et al (1998). Prognostic value of Cyclin E and p53 expression in gastric carcinoma. Cancer, 82, 1238-43. https://doi.org/10.1002/(SICI)1097-0142(19980401)82:7<1238::AID-CNCR5>3.0.CO;2-B
  19. Sumiyoshi Y, Kakeji Y, Egashira A, et al (2006). Overexpression of hypoxia-inducible factor 1alpha and p53 is a marker for an unfavorable prognosis in gastric cancer. Clin Cancer Res, 12, 5112-17. https://doi.org/10.1158/1078-0432.CCR-05-2382
  20. Williams ED, Sandler M (1963). The classification of carcinoid tum ours. Lancet, 1, 238-39.

Cited by

  1. Analysis on the Characteristics and Prognosis of Pulmonary Neuroendocrine Tumors vol.15, pp.5, 2014, https://doi.org/10.7314/APJCP.2014.15.5.2205
  2. Somatostatin Receptor 2 and 5 Expressions in Gastroenteropancreatic Neuroendocrine Tumors in Turkey vol.16, pp.10, 2015, https://doi.org/10.7314/APJCP.2015.16.10.4377
  3. Overexpression of Cyclin E and its Low Molecular Weight Isoforms Cooperate with Loss of p53 in Promoting Oncogenic Properties of MCF-7 Breast Cancer Cells vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7575
  4. Inhibits Proliferation and Mediates Suppression of Migration via DLC1/RhoA Signaling in Cancer Cells vol.16, pp.4, 2015, https://doi.org/10.7314/APJCP.2015.16.4.1637