Abstract
The purpose of this study was to investigate the expression of autophagy-related proteins Beclin 1 and LC3 in cervical normal epithelial cells and squamous cancer cells, and to evaluate the prognostic significance of Beclin 1 and LC3 expression in FIGO stage I–II cervical squamous cell carcinoma. The immunohistochemical expression of Beclin 1 and LC3 were evaluated in 26 formalin-fixed paraffin-embedded cervical normal tissue samples and 50 tumor samples of FIGO stage I–II cervical squamous cell carcinoma, respectively. Correlations with clinicopathologic characteristics were determined by Chi-square test. The prognostic impact of Beclin 1 and LC3 expression in regard to overall survival was determined by Kaplan–Meier method. Cervical normal squamous epithelial cells and cancer cells expressed high Beclin 1 immunoreactivity in 96.2 % (25/26) and 28.0 % (14/50) of patients (p = 0.000), and expressed high LC3 immunoreactivity in 76.9 % (20/26) and 26.0 % (13/50) of patients, respectively (p = 0.000). The expression of both Beclin 1 and LC3 were not associated with age, FIGO stage, pathologic differentiation, and lymph node metastasis. The 3-year overall survival (OS) rates with low and high expressions of Beclin 1 were 72.2 and 100.0 %, respectively (p = 0.034). The 3-year OS rates with low and high expressions of LC3 were 75.7 and 92.3 %, respectively (p = 0.224). These results show that expression level of both Beclin-1 and LC3 were significantly lower in cervical squamous cancer cells than normal squamous epithelial cells. The expression of Beclin 1 and LC3 may have prognostic significance in early stage cervical squamous cell carcinoma.
Similar content being viewed by others
References
Sun Y, Liu JH, Jin L, et al. Over-expression of the Beclin1 gene upregulates chemosensitivity to anti-cancer drugs by enhancing therapy-induced apoptosis in cervix squamous carcinoma CaSki cells. Cancer Lett. 2010;294:204–10.
Komaki R, Brickner TJ, Hanlon AL, et al. Long-term results of treatment of cervical carcinoma in the United States in 1973, 1978 and 1983: patterns of care study (PCS). Int J Radiat Oncol Biol Phys. 1995;31:973–82.
Jermal A, Siegel R, Ward E. Cancer statistics. CA Cancer J Clin. 2009;59:225–49.
Lee YY, Choi CH, Kim CJ, et al. The prognostic significance of the SUVmax (maximum standardized uptake value for F-18 fluorodeoxyglucose) of the cervical tumor in PET imaging for early cervical cancer: preliminary results. Gynecol Oncol. 2009;115:65–8.
Kim BS, Kim IJ, Kim SJ, et al. The prognostic value of the metabolic tumor volume in FIGO stage IA to IIB cervical cancer for tumor recurrence: measured by F-18 FDG PET/CT. Nucl Med Mol Imaging. 2011;45:36–42.
Eisenberg-Lerner A, Kimchi A. The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis. 2009;14:376–91.
Zois CE, Koukourakis MI. Radiation-induced autophagy in normal and cancer cells: towards novel cytoprotection and radio-sensitization policies? Autophagy. 2009;5:442–50.
Sivridis E, Koukourakis MI, Mendrinos SE, et al. Beclin-1 and LC3A expression in cutaneous malignant melanomas: a biphasic survival pattern for beclin-1. Melanoma Res. 2011;21:188–95.
Karpathiou G, Sivridis E, Koukourakis MI, et al. Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas. Chest. 2011;140:127–34.
Cheong H, Klionsky DJ. Biochemical methods to monitor autophagy-related processes in yeast. Methods Enzymol. 2008;451:1–26.
Eskelinen EL, Saftig P. Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 2009;1793:664–73.
Miracco C, Meng GC, Franchi A, et al. Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions. Human Pathol. 2010;41:503–12.
Klionsky DJ, Abeliovich H, Agostinis P, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in high eukaryotes. Autophagy. 2008;4:151–75.
Ding ZB, Shi YH, Zhou J, et al. Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma. Cancer Res. 2008;68:9167–75.
Chen YB, Hou JH, Feng XY, et al. Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas. J Surg Oncol. 2012;105:542–7.
Giatromanolaki A, Koukourakis MI, Koutsopoulos A, et al. High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas. Gynecol Oncol. 2011;123:147–51.
Sivridis E, Koukourakis MI, Zois CE, et al. LC3A-positive light microscopy detected patterns of autophagy and prognosis in operable breast carcinomas. Am J Pathol. 2010;176:2477–89.
Chen Y, Lu Y, Lu C, et al. Beclin-1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (HIF)-1α expression. Pathol Oncol Res. 2009;15:487–93.
Jiang ZF, Shao LJ, Wang WM, et al. Decreased expression of Beclin-1 and LC3 in the human lung cancer. Mol Biol Rep. 2012;39:259–67.
Aoki H, Kondo Y, Aldape K, et al. Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy. 2008;4:467–75.
Shen Y, Li DD, Wang LL, et al. Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy. 2008;16:1067–8.
Yoshioka A, Miyata H, Doki Y, et al. LC3, an autophagosome marker, is highly expressed in gastrointestinal cancer. Int J Oncol. 2008;33:461–8.
Liang XH, Kleeman LK, Jiang HH, et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol. 1998;72:8586–96.
Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumor hypoxia. Br J Cancer. 2010;103:1209–14.
Fujii S, Mitsunaga S, Yamazaki M, et al. Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci. 2008;99:1813–9.
Cheng HY, Zhang YN, Wu QL, et al. Expression and clinical significance of LC3 in cervical cancer tissues. Chin J Cancer Prev Treat. 2011;18:1247–51.
Acknowledgments
This study was supported by grants from the Priority Academic Program Development of Jiangsu Higher Education Institutions and Jiangsu Province’s Key Medical Department in 2011.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, W., Pan, X., Li, F. et al. Expression of Beclin 1 and LC3 in FIGO stage I–II cervical squamous cell carcinoma and relationship to survival. Tumor Biol. 33, 1653–1659 (2012). https://doi.org/10.1007/s13277-012-0421-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-012-0421-4