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Expression of Ki-67, p53 and VEGF in Pediatric Neuroblastoma

  • Gheytanchi, Elmira (Oncopathology Research Center, Iran University of Medical Sciences) ;
  • Mehrazma, Mitra (Oncopathology Research Center, Iran University of Medical Sciences) ;
  • Madjd, Zahra (Oncopathology Research Center, Iran University of Medical Sciences)
  • 발행 : 2014.04.01

초록

Background: Neuroblastoma (NB), is a neuroectodermal tumor derived from neural crest cells, and it is the second most common pediatric malignant tumor. The biological and clinical behavior of NB is very heterogeneous. This study was conducted to evaluate the expression of Ki-67, p53 and VEGF markers in tissues obtained from NB patients with different histologic types and stage. Materials and Methods: Tissue microarray (TMA) blocks were constructed from paraffin blocks of the NB tissues. Immunohistochemical staining was performed on TMA sections to detect the expression of Ki-67, p53 and VEGF markers. The association between the expression of these markers and clinicopathological parameters were then analyzed. Results: We had 18 patients with NB, one patient with ganglioneuroblastoma (GNB) and one with ganglioneuroma. Ki-67 was expressed in 13 (65%) tumors, and negatively correlated with age, prognosis, histologic type and stage of NB (all p<0.05). High and moderate expression of VEGF was found in 5% (1/20) and 65% (13/20) of the tumors, respectively; and it was positively correlated with age, prognosis and histologic types (all p<0.05) and negatively correlated with MKI (mitosis-karyorrhexis index). p53 expression was observed in 10% (2/20) of the tumors, which showed a relative correlation with MKI (p value=0.07). Conclusions: VEGF as a candidate for anti-angiogenic targeted therapy was correlated with the development and progression of NB; therefore, VEGF along with Ki-67 can serve as a valuable marker for the prognosis of this tumor type.

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참고문헌

  1. Bukhari MH, Niazi S, Anwar M, Chaudhry NA, Naeem S (2008). Prognostic significance of new immunohistochemistry scoring of p53 protein expression in cutaneous squamous cell carcinoma of mice. Ann N Y Acad Sci, 1138, 1-9. https://doi.org/10.1196/annals.1414.001
  2. Castel V, Segura V, Berlanga P (2013). Emerging drugs for neuroblastoma. Expert Opin Emerg Drugs, 18, 155-71. https://doi.org/10.1517/14728214.2013.796927
  3. Cheung R (2012). Poor treatment outcome of neuroblastoma and other peripheral nerve cell tumors may be related to under usage of radiotherapy and socio-economic disparity: a US SEER data analysis. Asian Pac J Cancer Prev, 13, 4587-91. https://doi.org/10.7314/APJCP.2012.13.9.4587
  4. Chung YS, Maeda K, Sowa M (1996). Prognostic value of angiogenesis in gastro-intestinal tumours. Eur J Cancer, 32, 2501-5. https://doi.org/10.1016/S0959-8049(96)00382-6
  5. Davidoff AM, Pence JC, Shorter NA, Iglehart JD, Marks JR (1992). Expression of p53 in human neuroblastoma- and neuroepithelioma-derived cell lines. Oncogene, 7, 127-33.
  6. Del Carmen Mejia M, Navarro S, Pellin A, et al (2002). Study of proliferation and apoptosis in neuroblastoma. Their relation with other prognostic factors. Arch Med Res, 33, 466-72. https://doi.org/10.1016/S0188-4409(02)00384-3
  7. Ferrara N (2002). VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2, 795-803. https://doi.org/10.1038/nrc909
  8. Ferrara N, Gerber HP, LeCouter J (2003). The biology of VEGF and its receptors. Nat Med, 9, 669-76. https://doi.org/10.1038/nm0603-669
  9. Goldhirsch A, Ingle JN, Gelber RD, et al (2009). Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol, 20, 1319-29. https://doi.org/10.1093/annonc/mdp322
  10. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991). p53 mutations in human cancers. Science, 253, 49-53. https://doi.org/10.1126/science.1905840
  11. Imamura J, Bartram CR, Berthold F, et al (1993). Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification. Cancer Res, 53, 4053-8.
  12. Inandiklioglu N, Yilmaz S, Demirhan O, Erdogan S, Tanyeli A (2012). Chromosome imbalances and alterations of AURKA and MYCN genes in children with neuroblastoma. Asian Pac J Cancer Prev, 13, 5391-7. https://doi.org/10.7314/APJCP.2012.13.11.5391
  13. Ishola TA, Chung DH (2007). Neuroblastoma. Surg Oncol, 16, 149-56.
  14. Jakovljevic G, Culic S, Stepan J, Bonevski A, Seiwerth S (2009). Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis. J Exp Clin Cancer Res, 143, 1-11.
  15. Jin Q, Hemminki K, Enquist K, et al (2005). Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res, 11, 3647-53. https://doi.org/10.1158/1078-0432.CCR-04-1803
  16. Jonat W, Arnold N (2011). Is the Ki-67 labelling index ready for clinical use? Ann Oncol, 22, 500-2. https://doi.org/10.1093/annonc/mdq732
  17. Levine AJ, Momand J, Finlay CA (1991). The p53 tumour suppressor gene. Nature, 351, 453-6. https://doi.org/10.1038/351453a0
  18. Maae E, Nielsen M, Steffensen KD, et al (2011). Estimation of immunohistochemical expression of VEGF in ductal carcinomas of the breast. J Histochem Cytochem, 59, 750-60. https://doi.org/10.1369/0022155411412599
  19. Madjd Z, Karimi A, Molanae S, Asadi-Lari M (2011). BRCA1 protein expression level and CD44(+) phenotype in breast cancer patients. Cell J, 13, 155-62.
  20. Martin B, Paesmans M, Mascaux C, et al (2004). Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer, 91, 2018-25. https://doi.org/10.1038/sj.bjc.6602233
  21. Mehdiabadi GB, Arab E, Rafsanjani KA, Ansari S, Moinzadeh AM (2013). Neuroblastoma in Iran: an experience of 32 years at a referral childrens hospital. Asian Pac J Cancer Prev, 14, 2739-42. https://doi.org/10.7314/APJCP.2013.14.5.2739
  22. Mehrazma M, Madjd Z, Kalantari E, et al (2013). Expression of stem cell markers, CD133 and CD44, in pediatric solid tumors: a study using tissue microarray. Fetal Pediatr Pathol, 32, 192-204. https://doi.org/10.3109/15513815.2012.701266
  23. Mejia C, Navarro S, Pellin A, et al (2003). Prognostic significance of cell proliferation in human neuroblastoma: comparison with other prognostic factors. Oncol Rep, 10, 243-7.
  24. Mejia C, Pellin A, Navarro S, Castel V, Llombart-Bosch A (1999). A new mutation of the p53 gene in human neuroblastoma, not correlated with N-myc amplification. Int J Surgical Pathol, 7, 149-54. https://doi.org/10.1177/106689699900700304
  25. Meric JB (2007). Angiogenesis targeting in gastro-intestinal cancers. Bull Cancer, 94, 207-15.
  26. Miller CW, Simon K, Aslo A, et al (1992). p53 mutations in human lung tumors. Cancer Res, 52, 1695-8.
  27. Modak S, Cheung NK (2010). Neuroblastoma: Therapeutic strategies for a clinical enigma. Cancer Treat Rev, 36, 307-17. https://doi.org/10.1016/j.ctrv.2010.02.006
  28. Mohsenzadegan M, Madjd Z, Asgari M, et al (2013). Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis. Cancer Immun Immunot, 62, 1609-18. https://doi.org/10.1007/s00262-013-1463-1
  29. Mueller S, Bhargava S, Molinaro AM, et al (2013). Poly (ADP-Ribose) polymerase inhibitor MK-4827 together with radiation as a novel therapy for metastatic neuroblastoma. Anticancer Res, 33, 755-62.
  30. Nikiteas NI, Tzanakis N, Theodoropoulos G, et al (2007). Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. Gastric Cancer, 10, 12-7. https://doi.org/10.1007/s10120-006-0401-8
  31. Osman J, Galli S, Hanafy M, Tang X, Ahmed A (2013). Identification of novel biomarkers in neuroblastoma associated with the risk for bone marrow metastasis: a pilot study. Clin Transl Oncol, 15, 953-8. https://doi.org/10.1007/s12094-013-1030-4
  32. Owens C, Irwin M (2012). Neuroblastoma: the impact of biology and cooperation leading to personalized treatments. Crit Rev Clin Lab Sci, 49, 85-115. https://doi.org/10.3109/10408363.2012.683483
  33. Patterson DM, Gao D, Trahan DN, et al (2011). Effect of MDM2 and vascular endothelial growth factor inhibition on tumor angiogenesis and metastasis in neuroblastoma. Angiogenesis, 14, 255-66. https://doi.org/10.1007/s10456-011-9210-8
  34. Pistoia V, Morandi F, Bianchi G, et al (2013). Immunosuppressive microenvironment in neuroblastoma. Front Oncol, 3, 1-8.
  35. Remvikos Y, Beuzeboc P, Zajdela A, et al (1989). Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy. J Natl Cancer Inst, 81, 1383-7. https://doi.org/10.1093/jnci/81.18.1383
  36. Sayed-Ahmed MM, Hafez MM, Al-Shabanah OA, et al (2013). Increased expression of biological markers as potential therapeutic targets in Saudi women with triple-negative breast cancer. Tumori, 99, 545-54. https://doi.org/10.1177/030089161309900418
  37. Scholzen T, Gerdes J (2000). The Ki-67 protein: from the known and the unknown. J Cell Physiol, 182, 311-22. https://doi.org/10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9
  38. Shimada H, Ambros IM, Dehner LP, et al (1999). Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee. Cancer, 86, 349-63. https://doi.org/10.1002/(SICI)1097-0142(19990715)86:2<349::AID-CNCR20>3.0.CO;2-Y
  39. Sidell N, Koeffler HP (1988). Modulation of Mr 53,000 protein with induction of differentiation of human neuroblastoma cells. Cancer Res, 48, 2226-30.
  40. Taeb J, Asgari M, Abolhasani M, Farajollahi MM, Madjd Z (2014). Expression of prostate stem cell antigen (PSCA) in prostate cancer: A tissue microarray study of Iranian patients. Pathol Res Pract, 210, 18-23. https://doi.org/10.1016/j.prp.2013.09.012
  41. Teitz T, Inoue M, Valentine MB, et al (2013). Th-MYCN mice with caspase-8 deficiency develop advanced neuroblastoma with bone marrow metastasis. Cancer Res, 73, 4086-97. https://doi.org/10.1158/0008-5472.CAN-12-2681
  42. Tong QS, Zheng LD, Tang ST, et al (2008). Expression and clinical significance of stem cell marker CD133 in human neuroblastoma. World J Pediatr, 4, 58-62. https://doi.org/10.1007/s12519-008-0012-z
  43. Tweddle DA, Pearson AD, Haber M, et al (2003). The p53 pathway and its inactivation in neuroblastoma. Cancer Lett, 197, 93-8. https://doi.org/10.1016/S0304-3835(03)00088-0
  44. Wang X, Chen X, Fang J, Yang C (2013). Overexpression of both VEGF-A and VEGF-C in gastric cancer correlates with prognosis, and silencing of both is effective to inhibit cancer growth. Int J Clin Exp Pathol, 6, 586-97.
  45. Yamamori M, Sakaeda T, Nakamura T, et al (2004). Association of VEGF genotype with mRNA level in colorectal adenocarcinomas. Biochem Biophys Res Commun, 325, 144-50. https://doi.org/10.1016/j.bbrc.2004.10.005
  46. Zhang J, Liu Y, Bao P, Wang Y, Zhang Y (2013). Rare coexistence of metastatic neuroblastoma of liver and solid pseudo papillary tumor of pancreas: Case report and literature review. J Cancer Res Ther, 9, 308-10. https://doi.org/10.4103/0973-1482.113402

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