Expression of Cyclin D1 Protein in Stage T2-3N0M0 Esophageal Carcinoma and Its Relationship with Prognosis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANGDong-kun ¹ , SUXiao-dong ² , ZHANGXu ² , HUYi ² ,  RONGTie-hua ²

1. Department of Thoracic Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P. R. China;
2. Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China;

Corresponding author：

RONGTie-hua, Email: rongth@sysucc.org.cn

Keywords：

Esophageal squamous cell carcinoma; Cyclin D1; Immunohistochemistry; Prognosis

DOI：

10.7507/1007-4848.20140014

Video：

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Objective To investigate the expression of Cyclin D1 in stage T_2-3N₀M₀ esophageal squamous cell carcinoma (ESCC) and its relationship with patient prognosis. Methods Expression of Cyclin D1 in 227 ESCC specimens at stage T_2-3N₀M₀ was detected by immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve analysis was performed to select the cut-off score for high or low IHC reactivity. Correlations between Cyclin D1 expression and clinicopathological features as well as prognosis of ESCC patients were determined. Results Among the 227 patients, 90 (39.6%) patients had low expression of Cyclin D1, and 137 (60.4%) patients had high expression of Cyclin D1.No significant correlation was observed between Cyclin D1 expression and patient gender (P=0.298), age(P=0.525), tumor location (P=0.570), tumor length (P=0.056), tumor grade (P=0.713), and depth of invasion (P=0.557). There was significant difference in prognosis between low-expression Cyclin D1 group and high-expression Cyclin D1 group (3-year survival rate:51.1% vs. 43.8%, 5-year survival rate:43.3% vs. 30.7%, P=0.047). Cox proportional-hazards regression model analysis showed that Cyclin D1 was not an independent prognostic factor for ESCC patients at stage T_2-3N₀M₀ (relative risk=1.378, 95% CI:0.990-1.919, P=0.057). Conclusion Over expression of Cyclin D1 may be an adverse prognostic factor of ESCC patients at stage T_2-3N₀M₀.

Citation： ZHANGDong-kun, SUXiao-dong, ZHANGXu, HUYi, RONGTie-hua. Expression of Cyclin D1 Protein in Stage T_2-3N₀M₀ Esophageal Carcinoma and Its Relationship with Prognosis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(1): 47-51. doi: 10.7507/1007-4848.20140014 Copy

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2.	Sherr CJ.G1 phase progression:cycling on cue.Cell, 1994, 79 (4):551-555.
3.	Lin RJ, Lubpairee T, Liu KY, et al.Cyclin D1 overexpression is associated with poor prognosis in oropharyngeal cancer.J Otolaryngol Head Neck Surg, 2013, 42 (1):23.
4.	Che Y, Ye F, Xu R, et al.Co-expression of XIAP and cyclin D1 complex correlates with a poor prognosis in patients with hepatocellular carcinoma.Am J Pathol, 2012, 180 (5):1798-1807.
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6.	Huang SF, Cheng SD, Chuang WY, et al.Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma.World J Surg Oncol, 2012, 10 (2):40.
7.	Barbieri F, Lorenzi P, Ragni N, et al.Overexpression of cyclin D1 is associated with poor survival in epithelial ovarian cancer.Oncology, 2004, 66 (4):310-315.
8.	Zhu ZH, Sun BY, Ma Y, et al.Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung Cancer.J Clin Oncol, 2009, 27 (7):1091-1099.
9.	Zlobec I, Steele R, Terracciano L, et al.Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer.J Clin Pathol, 2007, 60 (10):1112-1116.
10.	杜雅丽, 李道帆, 李静.用ROC曲线评价心血管病危险因素聚集的相关因素及适宜切点的确定.广东医学, 2003, 24 (9):993-995.
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20.	Anayama T, Furihata M, Ishikawa T, et al.Positive correlation between p27Kip1 expression and progression of human esophageal squamous cell carcinoma.Int J Cancer, 1998, 79 (4):439-443.
21.	Fukuchi M, Fukai Y, Kimura H, et al.Prolyl isomerase Pin1 expression predicts prognosis in patients with esophageal squamous cell carcinoma and correlates with cyclin D1 expression.Int J Oncol, 2006, 29 (2):329-334.
22.	Güner D, Sturm I, Hemmati P, et al.Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis.Int J Cancer, 2003, 103 (4):445-454.
23.	Ikeguchi M, Sakatani T, Ueta T, et al.Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma.J Cancer Res Clin Oncol, 2001, 127 (9):531-536.
24.	Kuwahara M, Hirai T, Yoshida K, et al.p53, p21 (Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer.Dis Esophagus, 1999, 12 (2):116-119.
25.	Sarbia M, Stahl M, Fink U, et al.Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities.Int J Cancer, 1999, 84 (1):86-91.
26.	Shinohara M, Aoki T, Sato S, et al.Cell cycle-regulated factors in esophageal cancer.Dis Esophagus, 2002, 15 (2):149-154.
27.	孙爱民, 李道堂, 穆殿斌, 等.食管鳞癌组织Cyclin D1和Ki-67表达及其与预后相关性的研究.中华肿瘤防治杂志, 2008, 15 (4):276-279.
28.	Masayuki I, Yutaka S, Hiroko I, et al.Prognostic significance of cyclin D1 and E-cadherin in patients with esophageal squamous cell carcinoma:multiinstitutional retrospective analysis.Research committee on malignancy of esophageal cancer, Japanese society for esophageal diseases.J Am Coll Surg, 2001, 192 (6):708-718.

1. Marx J.How cells cycle toward cancer.Science, 1994, 263 (5145):319-321.
2. Sherr CJ.G1 phase progression:cycling on cue.Cell, 1994, 79 (4):551-555.
3. Lin RJ, Lubpairee T, Liu KY, et al.Cyclin D1 overexpression is associated with poor prognosis in oropharyngeal cancer.J Otolaryngol Head Neck Surg, 2013, 42 (1):23.
4. Che Y, Ye F, Xu R, et al.Co-expression of XIAP and cyclin D1 complex correlates with a poor prognosis in patients with hepatocellular carcinoma.Am J Pathol, 2012, 180 (5):1798-1807.
5. Tsai HL, Yeh YS, Chang YT, et al.Co-existence of cyclin D1 and vascular endothelial growth factor protein expression is a poor prognostic factor for UICC stage Ⅰ-Ⅲ colorectal Cancer patients after curative resection.J Surg Oncol, 2013, 107 (2):148-154.
6. Huang SF, Cheng SD, Chuang WY, et al.Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma.World J Surg Oncol, 2012, 10 (2):40.
7. Barbieri F, Lorenzi P, Ragni N, et al.Overexpression of cyclin D1 is associated with poor survival in epithelial ovarian cancer.Oncology, 2004, 66 (4):310-315.
8. Zhu ZH, Sun BY, Ma Y, et al.Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung Cancer.J Clin Oncol, 2009, 27 (7):1091-1099.
9. Zlobec I, Steele R, Terracciano L, et al.Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer.J Clin Pathol, 2007, 60 (10):1112-1116.
10. 杜雅丽, 李道帆, 李静.用ROC曲线评价心血管病危险因素聚集的相关因素及适宜切点的确定.广东医学, 2003, 24 (9):993-995.
11. Donnellan R, Chetty R.Cyclin D1 and human neoplasia.Mol Pathol, 1998, 51 (1):1-7.
12. Le Marchand L, Seifried A, Lum-Jones A, et al.Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer.JAMA, 2003, 290 (21):2843-2848.
13. Recchia AG, Musti AM, Lanzino M, et al.A cross-talk between the androgen receptor and the epidermal growth factor receptor leads to p38MAPK-dependent activation of mTOR and cyclinD1 expression in prostate and lung cancer cells.Int J Biochem Cell Biol, 2009, 41 (3):603-614.
14. Liu B, Ren Z, Shi Y, et al.Activation of signal transducers and activators of transcription 3 and overexpression of its target gene CyclinD1 in laryngeal carcinomas.Laryngoscope, 2008, 118 (11):1976-1980.
15. Nagasawa S, Onda M, Sasajima K, et al.Cyclin D1 overexpression as aprognostic factor in patients w ith esophageal carcinoma.J Surg Oncol, 2001, 78 (3):208-214.
16. 张旭, 黄晓平, 马国伟, 等.Cyclin D1在食管癌中的表达及其临床意义.中山大学学报:医学科学版, 2006, 27 (6):657-660, 693.
17. Itami A, Shimada Y, Watanabe G, et al.Prognostic value of p27 (Kip1) and CyclinD1 expression in esophageal cancer.Oncology, 1999, 57 (4):311-317.
18. Shiozaki H, Doki Y, Yamana H, et al.A multi-institutional study of immunohistochemical investigation for the roles of cyclin D1 and E-cadherin in superficial squamous cell carcinoma of the esophagus.J Surg Oncol, 2002, 79 (3):166-173.
19. Zhao J, Li L, Wei S, et al.Clinicopathological and prognostic role of cyclin D1 in esophageal squamous cell carcinoma:a meta-analysis.Dis Esophagus, 2012, 25 (6):520-526.
20. Anayama T, Furihata M, Ishikawa T, et al.Positive correlation between p27Kip1 expression and progression of human esophageal squamous cell carcinoma.Int J Cancer, 1998, 79 (4):439-443.
21. Fukuchi M, Fukai Y, Kimura H, et al.Prolyl isomerase Pin1 expression predicts prognosis in patients with esophageal squamous cell carcinoma and correlates with cyclin D1 expression.Int J Oncol, 2006, 29 (2):329-334.
22. Güner D, Sturm I, Hemmati P, et al.Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis.Int J Cancer, 2003, 103 (4):445-454.
23. Ikeguchi M, Sakatani T, Ueta T, et al.Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma.J Cancer Res Clin Oncol, 2001, 127 (9):531-536.
24. Kuwahara M, Hirai T, Yoshida K, et al.p53, p21 (Waf1/Cip1) and cyclin D1 protein expression and prognosis in esophageal cancer.Dis Esophagus, 1999, 12 (2):116-119.
25. Sarbia M, Stahl M, Fink U, et al.Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities.Int J Cancer, 1999, 84 (1):86-91.
26. Shinohara M, Aoki T, Sato S, et al.Cell cycle-regulated factors in esophageal cancer.Dis Esophagus, 2002, 15 (2):149-154.
27. 孙爱民, 李道堂, 穆殿斌, 等.食管鳞癌组织Cyclin D1和Ki-67表达及其与预后相关性的研究.中华肿瘤防治杂志, 2008, 15 (4):276-279.
28. Masayuki I, Yutaka S, Hiroko I, et al.Prognostic significance of cyclin D1 and E-cadherin in patients with esophageal squamous cell carcinoma:multiinstitutional retrospective analysis.Research committee on malignancy of esophageal cancer, Japanese society for esophageal diseases.J Am Coll Surg, 2001, 192 (6):708-718.

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Expression of Cyclin D1 Protein in Stage T_2-3N₀M₀ Esophageal Carcinoma and Its Relationship with Prognosis

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