Expression of cell cycle related proteins cyclin D1, p53 and p21 in esophageal squamous cell carcinoma
Received date: 2010-01-15
Revised date: 2010-03-14
Online published: 2010-05-15
Dysregulation of cell cycle control, especially G1/S phase transition, is implicated in the pathogenesis of most human cancers, including esophageal squamous cell carcinoma (ESCC). However, the clinicopathological significance of aberrant expression of G1/S phase-related proteins in ESCC remains unclear. In the present study, cyclin D1, p21WAF1/Cip1 and p53 protein expression were examined in 148 ESCC cases using immunohistochemistry combined with tissue microarray. We then analyzed the correlations between their expression and clinicopathological parameters and found that overexpression of p53 was associated with lymph node metastasis (P = 0.001). p21WAF1/Cip1 down-regulation was an independent prognostic factor by multivariate analysis (RR = 0.418, P <0 .001). Further more, array-CGH results revealed that cyclin D1 gene was amplified in 45.4% of ESCC patients. This study confirms that dysregulation of G1/S related genes is common in ESCC and reduced expression of p21WAF1/Cip1 protein can predict shorter overall survival time of patients with ESCC.
LIN De-Chen, SHI Zhi-Zhou, XUE Li-Yan, CHEN Wei, XU Cuan, HAN E-Ling, LV Ning, WANG Meng-Rong . Expression of cell cycle related proteins cyclin D1, p53 and p21 in esophageal squamous cell carcinoma[J]. Hereditas(Beijing), 2010 , 32(5) : 455 -460 . DOI: 10.3724/SP.J.1005.2010.00455
[1] Roncalli M, Bosari S, Marchetti A, Buttitta F, Bossi P, Graziani D, Peracchia A, Bonavina L, Viale G, Coggi G. Cell cycle-related gene abnormalities and product expression in esophageal carcinoma. Lab Invest, 1998, 78(9): 1049–1057.
[2] Shao L, Hittelman WN, Lin J, Yang H, Ajani JA, Wu X. Deficiency of cell cycle checkpoints and DNA repair sys-tem predispose individuals to esophageal cancer. Mutat Res, 2006, 602(1–2): 143–150.
[3] Shinohara M, Aoki T, Sato S, Takagi Y, Osaka Y, Koyanagi Y, Hatooka S, Shinoda M. Cell cycle-regulated factors in eso-phageal cancer. Dis Esophagus, 2002, 15(2): 149–154.
[4] Paulson TG, Galipeau PC, Xu L, Kissel HD, Li X, Blount PL, Sanchez CA, Odze RD, Reid BJ. p16 mutation spec-trum in the premalignant condition Barrett's esophagus. PloS One, 2008, 3(11): e3809.
[5] Fang JY, Lu YY. Effects of histone acetylation and DNA methylation on p21( WAF1) regulation. World J Gastro-enterol, 2002, 8(3): 400–405.
[6] Amanullah A, Hoffman B, Liebermann DA. Deregulated E2F-1 blocks terminal differentiation and loss of leuke-mogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and p16(INK4A). Blood, 2000, 96(2): 475–482.
[7] Zhang G, Zhou X, Xue L, Quan L, Wang Y, Zhou C, Lu N, Wang Q, Zhu H, Xu N. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int, 2005, 55(6): 310–317.
[8] Natsugoe S, Nakashima S, Matsumoto M, Xiangming C, Okumura H, Kijima F, Ishigami S, Takebayashi Y, Baba M, Takao S, Aikou T. Expression of p21WAF1/Cip1 in the p53-dependent pathway is related to prognosis in patients with advanced esophageal carcinoma. Clin Cancer Res, 1999, 5(9): 2445–2449.
[9] Mega S, Miyamoto M, Ebihara Y, Takahashi R, Hase R, Li L, Shichinohe T, Kawarada Y, Uehara H, Kaneko H, Hashimoto H, Murakami Y, Itoh T, Morikawa T, Kondo S. Cyclin D1, E2F1 expression levels are associated with characteristics and prognosis of esophageal squamous cell carcinoma. Dis Esophagus, 2005, 18(2): 109–113.
[10] Wei F, Ni J, Wu SS, Liu H, Xu X, Han YL, Cai Y, Zhang JW, Chen XJ, Pang H, Lu N, Ji L, Wu M, Wang MR. Cytogenetic studies of esophageal squamous cell carcinomas in the north-ern Chinese population by comparative genomic hybridiza-tion. Cancer Genet Cytogenet, 2002, 138(1): 38–43.
[11] He YT, Hou J, Qiao CY, Chen ZF, Song GH, Li SS, Meng FS, Jin HX, Chen C. An analysis of esophageal cancer in-cidence in Cixian county from 1974 to 1996. World J Gastroenterol, 2003, 9(2): 209–213.
[12] Pesutic-Pisac V, Punda A, Gluncic I, Bedekovic V, Pranic-Kragic A, Kunac N. Cyclin D1 and p27 expression as prognostic factor in papillary carcinoma of thyroid: as-sociation with clinicopathological parameters. Croat Med J, 2008, 49(5): 643–649.
[13] Aaltonen K, Amini RM, Landberg G, Eerola H, Aittomaki K, Heikkila P, Nevanlinna H, Blomqvist C. Cyclin D1 ex-pression is associated with poor prognostic features in es-trogen receptor positive breast cancer. Breast Cancer Res Treat, 2009, 113(1): 75–82.
[14] Ikeguchi M, Sakatani T, Ueta T, Kaibara N. Cyclin D1 expression and retinoblastoma gene protein (pRB) expres-sion in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol, 2001, 127(9): 531–536.
[15] Nakamura T, Ide H, Eguchi R, Hayashi K, Takasaki K. Concomitant analysis of p16/INK4, cyclin D1, and retino-blastoma protein expression in esophageal squamous cell car-cinoma. Hepatogastroenterology, 2003, 50(53): 1321–1326.
[16] Jang KT, Chae SW, Sohn JH, Park HR, Shin HS. Coex-pression of MUC1 with p53 or MUC2 corr
/
| 〈 |
|
〉 |