Expression of p16 and Survivin in gliomas and their correlation with cell proliferation

Gao,Yansheng; Li,Lingzhen; Song,Laijun

doi:10.3892/ol.2015.3180

Expression of p16 and Survivin in gliomas and their correlation with cell proliferation

Authors:
- Yansheng Gao
- Lingzhen Li
- Laijun Song
View Affiliations

Affiliations: Department of Neurosurgery Ⅱ, Zhumadian Central Hospital, Zhumadian, Henan 463000, P.R. China, Department of Neurology Ⅲ, Zhumadian Central Hospital, Zhumadian, Henan 463000, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: May 6, 2015 https://doi.org/10.3892/ol.2015.3180
Pages: 301-306

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The survival rate of glioma patients is very low, and a lack of effective diagnostic techniques are available at present. The current study aimed to investigate the expression of p16 and Survivin and their association with proliferation and apoptosis in gliomas, as well as patient characteristics and prognosis. In total, 62 glioma specimens were surgically resected and pathologically confirmed at the Zhumadian Central Hospital (Zhumadian, China) between June 2008 and February 2014. Clinical data, including the gender and age of the patients, as well as the location, infiltration degree, size and pathological stage of the glioma, was collected. In order to evaluate the expression of p16 and Survivin in the gliomas, the Ki‑67 labeling index was used to evaluate cell proliferation activity. The number of argyrophilic nucleolar organizer regions and the rate of cellular apoptosis was examined using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. The results were analyzed using SPSS 14.0 statistical software. The positive rate of p16 gene expression in the gliomas was 46.77% (29 cases), and p16 gene expression was positively correlated with the differentiation status, tumor size and pre-operative symptoms. The positive rate of Survivin expression in the gliomas was 69.88% (58 cases), and Survivin expression was positively correlated with tumor size, differentiation status and clinical stage. The proliferation activity of the gliomas was enhanced with increasing p16 and Survivin expression, while apoptosis was inhibited. In conclusion, the overexpression of p16 and Survivin was closely associated with uncontrolled cell proliferation and the inhibition of apoptosis in gliomas. The combined analysis of the expression of p16 and Survivin in gliomas may provide guidance with respect to the clinical diagnosis, evaluation, treatment and prognosis of patients with glioma.

View Figures

View References

1	Roci E, Cakani B, Brace G, Bushati T, Rroji A, Petrela M and Kaloshi G: Platinum-based chemotherapy in recurrent high-grade glioma patients: Retrospective study. Med Arch. 68:140–143. 2014. View Article : Google Scholar : PubMed/NCBI
2	Feng B, Hu P, Lu SJ, Chen JB and Ge RL: Increased argonaute 2 expression in gliomas and its association with tumor progression and poor prognosis. Asian Pac J Cancer Prev. 15:4079–4083. 2014. View Article : Google Scholar : PubMed/NCBI
3	Sai K, Yang QY, Shen D and Chen ZP: Chemotherapy for gliomas in mainland China: An overview. Oncol Lett. 5:1448–1452. 2013.PubMed/NCBI
4	Watts C, Price SJ and Santarius T: Current concepts in the surgical management of glioma patients. Clin Oncol (R Coll Radiol). 26:385–394. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ahmed R, Oborski MJ, Hwang M, Lieberman FS and Mountz JM: Malignant gliomas: Current perspectives in diagnosis, treatment and early response assessment using advanced quantitative imaging methods. Cancer Manag Res. 6:149–170. 2014.PubMed/NCBI
6	Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC and Cavenee WK: The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 61:215–225. 2002.PubMed/NCBI
7	Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J and Altieri DC: Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol. 152:43–49. 1998.PubMed/NCBI
8	Editorial Committee of Chinese Journal of Pathology: The meeting summary of the national symposium on immunohistochemical technique and diagnosis standard. Zhonghua Bing Li Xue Za Zhi. 25:326–328. 1996.(In Chinese).
9	Shankar SL, Mani S, O'Guin KN, Kandimalla ER, Agrawal S and Shafit-Zagardo B: Survivin inhibition induces human neural tumor cell death through caspase-independent and -dependent pathways. J Neurochem. 79:426–436. 2001.PubMed/NCBI
10	Parenti A, Leo G, Porzionato A, Zaninotto G, Rosato A and Ninfo V: Expression of survivin, p53 and caspase 3 in Barrett's esophagus carcinogenesis. Hum Pathol. 37:16–22. 2006. View Article : Google Scholar : PubMed/NCBI
11	Pan Y, Hu WH, Xie D, et al: Nuclear and cytoplasmic expressions of survivin in glioma and their prognostic value. Zhonghua Yi Xue Za Zhi. 87:325–329. 2007.(In Chinese). PubMed/NCBI
12	Ene CI and Holland EC: Personalized medicine for gliomas. Surg Neurol Int. 6(Suppl 1): S89–S95. 2015.PubMed/NCBI
13	Wilden JA, Voorhies J, Mosier KM, O'Neill DP and Cohen-Gadol AA: Strategies to maximize resection of complex, or high surgical risk, low-grade gliomas. Neurosurg Focus. 34:E52013. View Article : Google Scholar
14	Honda R, Körner R and Nigg EA: Exploring the functional interactions between Aurora B, INCENP and survivin in mitosis. Mol Biol Cell. 14:3325–3341. 2003. View Article : Google Scholar : PubMed/NCBI
15	Al-Khalaf HH, Lach B, Allam A, et al: Expression of survivin and p16(INK4a)/Cdk6/pRB proteins and induction of apoptosis in response to radiation and cisplatin in meningioma cells. Brain Res. 1188:25–34. 2008. View Article : Google Scholar : PubMed/NCBI
16	Chung CH, Zhang Q, Kong CS, et al: p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol. 32:3930–3938. 2014. View Article : Google Scholar : PubMed/NCBI
17	Kamb A: Role of a cell cycle regulator in hereditary and sporadic cancer. Cold Spring Harb Symp Quant Biol. 59:39–47. 1994. View Article : Google Scholar : PubMed/NCBI
18	Söling A, Plugge EM, Schmitz M, et al: Autoantibodies to the inhibitor of apoptosis protein survivin in patients with brain tumors. Int J Oncol. 30:123–128. 2007.PubMed/NCBI
19	Hassounah M, Lach B, Allam A, et al: Benign tumors from the human nervous system express high levels of survivin and are resistant to spontaneous and radiation-induced apoptosis. J Neurooncol. 72:203–208. 2005. View Article : Google Scholar : PubMed/NCBI
20	Bongiovanni L, Di Diodoro F, Della Salda L and Brachelente C: On the role of survivin as a stem cell biomarker of canine hair follicle and related tumours. Vet Dermatol. 25:138–141. 2014. View Article : Google Scholar : PubMed/NCBI
21	Khan S, Bennit HF, Turay D, Perez M, Mirshahidi S, Yuan Y and Wall NR: Early diagnostic value of survivin and its alternative splice variants in breast cancer. BMC Cancer. 14:1762014. View Article : Google Scholar : PubMed/NCBI
22	Kogiku M, Ohsawa I, Matsumoto K, Sugisaki Y, Takahashi H, Teramoto A and Ohta S: Prognosis of glioma patients by combined immunostaining for survivin, Ki-67 and epidermal growth factor receptor. J Clin Neurosci. 15:1198–1203. 2008. View Article : Google Scholar : PubMed/NCBI
23	Saito T, Arifin MT, Hama S, et al: Survivin subcellular localization in high-grade astrocytomas: Simultaneous expression in both nucleus and cytoplasm is negative prognostic marker. J Neurooncol. 82:193–198. 2007. View Article : Google Scholar : PubMed/NCBI
24	Nandi S, Ulasov IV, Tyler MA, et al: Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells. Cancer Res. 68:5778–5784. 2008. View Article : Google Scholar : PubMed/NCBI
25	Pennati M, Folini M and Zaffaroni N: Targeting survivin in cancer therapy. Expert Opin Ther Targets. 12:463–476. 2008. View Article : Google Scholar : PubMed/NCBI
26	Chen LH, Li YW, Gao LY and Liu JF: An evaluation for the function and significance concerned to alternations of p16 3D structure with gene mutation in esophageal squamous cell carcinoma. Chin J Med Genet. 23:208–212. 2006.
27	Selemetjev S, Dencic TI, Marecko I, Jankovic J, Paunovic I, Savin S and Cvejic D: Evaluation of survivin expression and its prognostic value in papillary thyroid carcinoma. Pathol Res Pract. 210:30–34. 2014. View Article : Google Scholar : PubMed/NCBI
28	Piaton E, Carré C, Advenier AS, et al: p16 INK4a overexpression and p16/Ki-67 dual labeling versus conventional urinary cytology in the evaluation of urothelial carcinoma. Cancer Cytopathol. 122:211–220. 2014. View Article : Google Scholar : PubMed/NCBI