Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.7.3065

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.7, 2014 , pp. 3065-3070 More about this Journal
Abstract
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.
Keywords
Ki-67; p53; VEGF; neuroblastoma;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 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.
2 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.   DOI   ScienceOn
3 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.   DOI
4 Tweddle DA, Pearson AD, Haber M, et al (2003). The p53 pathway and its inactivation in neuroblastoma. Cancer Lett, 197, 93-8.   DOI   ScienceOn
5 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.   DOI   ScienceOn
6 Pistoia V, Morandi F, Bianchi G, et al (2013). Immunosuppressive microenvironment in neuroblastoma. Front Oncol, 3, 1-8.
7 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.   DOI
8 Owens C, Irwin M (2012). Neuroblastoma: the impact of biology and cooperation leading to personalized treatments. Crit Rev Clin Lab Sci, 49, 85-115.   DOI   ScienceOn
9 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.   DOI   ScienceOn
10 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.   DOI
11 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.   DOI
12 Scholzen T, Gerdes J (2000). The Ki-67 protein: from the known and the unknown. J Cell Physiol, 182, 311-22.   DOI
13 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.   DOI
14 Sidell N, Koeffler HP (1988). Modulation of Mr 53,000 protein with induction of differentiation of human neuroblastoma cells. Cancer Res, 48, 2226-30.
15 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.   DOI   ScienceOn
16 Meric JB (2007). Angiogenesis targeting in gastro-intestinal cancers. Bull Cancer, 94, 207-15.
17 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.   DOI
18 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.   과학기술학회마을   DOI   ScienceOn
19 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.   DOI   ScienceOn
20 Miller CW, Simon K, Aslo A, et al (1992). p53 mutations in human lung tumors. Cancer Res, 52, 1695-8.
21 Modak S, Cheung NK (2010). Neuroblastoma: Therapeutic strategies for a clinical enigma. Cancer Treat Rev, 36, 307-17.   DOI   ScienceOn
22 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.   DOI   ScienceOn
23 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.
24 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.   DOI
25 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.   DOI   ScienceOn
26 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.
27 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.
28 Ishola TA, Chung DH (2007). Neuroblastoma. Surg Oncol, 16, 149-56.
29 Jonat W, Arnold N (2011). Is the Ki-67 labelling index ready for clinical use? Ann Oncol, 22, 500-2.   DOI   ScienceOn
30 Levine AJ, Momand J, Finlay CA (1991). The p53 tumour suppressor gene. Nature, 351, 453-6.   DOI   ScienceOn
31 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.   DOI   ScienceOn
32 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.
33 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.   DOI   ScienceOn
34 Chung YS, Maeda K, Sowa M (1996). Prognostic value of angiogenesis in gastro-intestinal tumours. Eur J Cancer, 32, 2501-5.   DOI   ScienceOn
35 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.
36 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.   DOI   ScienceOn
37 Castel V, Segura V, Berlanga P (2013). Emerging drugs for neuroblastoma. Expert Opin Emerg Drugs, 18, 155-71.   DOI   ScienceOn
38 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.   과학기술학회마을   DOI   ScienceOn
39 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.   DOI   ScienceOn
40 Ferrara N (2002). VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2, 795-803.   DOI   ScienceOn
41 Ferrara N, Gerber HP, LeCouter J (2003). The biology of VEGF and its receptors. Nat Med, 9, 669-76.   DOI   ScienceOn
42 Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991). p53 mutations in human cancers. Science, 253, 49-53.   DOI
43 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.   DOI   ScienceOn
44 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.   DOI
45 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.
46 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.   과학기술학회마을   DOI   ScienceOn