Protein Expression of RAS-association Domain Family 1A Gene and Its Significance in Patients with Vulvar Cancer_West China Medical Journal

Authors：

 WANGXue-ping ,  LIUHui

Department of Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LIUHui, Email: lh666888@163.com

Keywords：

Vulvar Cancer; Immunohistochemistry technology; RAS-association domain family 1A gene

DOI：

10.7507/1002-0179.20140387

Video：

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Objective To evaluate the relation between protein expression of RAS-association domain family 1A (RASSF1A) gene and the occurrence and development of vulvar cancer. Methods Immunohistochemistry was used to detect the expression of RASSF1A protein in 9 normal vulvar tissues, 12 vulvar intraepithelial neoplasm (VIN) tissues, as well as 35 vulvar cancer tissue samples which were taken from patients treated during January 2008 to December 2010. Then, we analyzed the correlation between the RASSF1A protein expression and the clinical pathological features of vulvar cancer. Results The expression of RASSF1A protein in vulvar cancer samples was significantly different from that in samples of normal vulvar tissues and VIN tissues (P<0.05). Significant difference also existed in the expression of RASSF1A protein between normal vulvar tissues and VIN tissues (P<0.05). The expression of RASSF1A protein was not significantly correlated with age, grade, stage, lymph nodes involvement and sites (lateral/median) of vulvar cancer (P>0.05). Conclusion Inactivation of RASSF1A gene involves in the occurrence of vulvar cancer but has no significant correlation with its development. There is no obvious correlation between cancer sites, onset ages and the expression of RASSF1A protein.

Citation： WANGXue-ping, LIUHui. Protein Expression of RAS-association Domain Family 1A Gene and Its Significance in Patients with Vulvar Cancer. West China Medical Journal, 2014, 29(7): 1263-1266. doi: 10.7507/1002-0179.20140387 Copy

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2.	Höckel M, Schmidt K, Bornmann K, et al. Vulvar field resection:novel approach to the surgical treatment of vulvar cancer based on ontogenetic anatomy[J]. Gynecol Oncol, 2010, 119(1):106-113.
3.	Richter AM, Pfeifer GP, Dammann RH. The RASSF proteins in cancer; from epigenetic silencing to functional characterization[J]. Biochim Biophys Acta, 2009, 1796(2):114-128.
4.	Mitra S, Mazumder Indra D, Basu PS, et al. Alterations of RASSF1A in premalignant cervical lesions:clinical and prognostic significance[J]. Mol Carcinog, 2012, 51(9):723-733.
5.	Maliukova AV, Loginov VI, Khodyrev DS, et al. Methylation of the putative tumor suppressor gene, RASSF1A, in primary cervical tumors[J]. Mol Biol (Mosk), 2004, 38(6):1005-1013.
6.	南芳芳, 姜洁, 夏敏, 等. RASSF1A基因在子宫内膜癌组织中的表达及意义[J]. 山东大学学报·医学版, 2007, 45(1):94-96, 100.
7.	Fiolka R, Zubor P, Janusicova V, et al. Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer[J]. Oncol Rep, 2013, 30(6):2878-2886.
8.	Shi H, Li Y, Wang X, et al. Association between RASSF1A promoter methylation and ovarian cancer:a meta-analysis[J]. PLoS One, 2013, 8(10):e76787.
9.	Zhang Q, Hu G, Yang Q, et al. A multiplex methylation-specific PCR assay for the detection of early-stage ovarian cancer using cell-free serum DNA[J]. Gynecol Oncol, 2013, 130(1):132-139.
10.	Dammann R, Li C, Yoon JH, et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3[J]. Nat Genet, 2000, 25(3):315-319.
11.	Knudson AG. Hereditary cancer:two hits revisited[J]. J Cancer Res Clin Oncol, 1996, 122(3):135-140.
12.	Agathanggelou A, Honorio S, Macartney DP, et al. Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours[J]. Oncogene, 2001, 20(12):1509-1518.
13.	沈亮, 张师前. RASSF1A基因甲基化与妇科肿瘤[J]. 国际肿瘤学杂志, 2008, 35(8):621-624.
14.	董延磊, 张师前. RASSF1A基因甲基化与妇科肿瘤发生发展的关系研究进展[J]. 山东医药, 2010, 50(26):111-112.
15.	Vos MD, Ellis CA, Bell A, et al. Ras uses the novel tumor suppressor RASSF1A as an effector to mediate apoptosis[J]. J Biol Chem, 2000, 275(46):35669-35672.
16.	Kim JH, Choi YD, Lee JS, et al. Quantitative assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens[J]. Virchows Arch, 2010, 457(1):35-42.
17.	Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:mechanistic studies and their implications for cancer therapy[J]. Oncogene, 2002, 21(35):5483-5495.
18.	Steiner M, Clark B, Tang JZ, et al. 14-3-3σ mediates G2-M arrest produced by 5-aza-2'-deoxycytidine and possesses a tumor suppressor role in endometrial carcinoma cells[J]. Gynecol Oncol, 2012, 127(1):231-240.

1. Schuurman MS, van Den Einden LC, Massuger LF, et al. Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma[J]. Eur J Cancer, 2013, 49(18):3872-3880.
2. Höckel M, Schmidt K, Bornmann K, et al. Vulvar field resection:novel approach to the surgical treatment of vulvar cancer based on ontogenetic anatomy[J]. Gynecol Oncol, 2010, 119(1):106-113.
3. Richter AM, Pfeifer GP, Dammann RH. The RASSF proteins in cancer; from epigenetic silencing to functional characterization[J]. Biochim Biophys Acta, 2009, 1796(2):114-128.
4. Mitra S, Mazumder Indra D, Basu PS, et al. Alterations of RASSF1A in premalignant cervical lesions:clinical and prognostic significance[J]. Mol Carcinog, 2012, 51(9):723-733.
5. Maliukova AV, Loginov VI, Khodyrev DS, et al. Methylation of the putative tumor suppressor gene, RASSF1A, in primary cervical tumors[J]. Mol Biol (Mosk), 2004, 38(6):1005-1013.
6. 南芳芳, 姜洁, 夏敏, 等. RASSF1A基因在子宫内膜癌组织中的表达及意义[J]. 山东大学学报·医学版, 2007, 45(1):94-96, 100.
7. Fiolka R, Zubor P, Janusicova V, et al. Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer[J]. Oncol Rep, 2013, 30(6):2878-2886.
8. Shi H, Li Y, Wang X, et al. Association between RASSF1A promoter methylation and ovarian cancer:a meta-analysis[J]. PLoS One, 2013, 8(10):e76787.
9. Zhang Q, Hu G, Yang Q, et al. A multiplex methylation-specific PCR assay for the detection of early-stage ovarian cancer using cell-free serum DNA[J]. Gynecol Oncol, 2013, 130(1):132-139.
10. Dammann R, Li C, Yoon JH, et al. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3[J]. Nat Genet, 2000, 25(3):315-319.
11. Knudson AG. Hereditary cancer:two hits revisited[J]. J Cancer Res Clin Oncol, 1996, 122(3):135-140.
12. Agathanggelou A, Honorio S, Macartney DP, et al. Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours[J]. Oncogene, 2001, 20(12):1509-1518.
13. 沈亮, 张师前. RASSF1A基因甲基化与妇科肿瘤[J]. 国际肿瘤学杂志, 2008, 35(8):621-624.
14. 董延磊, 张师前. RASSF1A基因甲基化与妇科肿瘤发生发展的关系研究进展[J]. 山东医药, 2010, 50(26):111-112.
15. Vos MD, Ellis CA, Bell A, et al. Ras uses the novel tumor suppressor RASSF1A as an effector to mediate apoptosis[J]. J Biol Chem, 2000, 275(46):35669-35672.
16. Kim JH, Choi YD, Lee JS, et al. Quantitative assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens[J]. Virchows Arch, 2010, 457(1):35-42.
17. Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:mechanistic studies and their implications for cancer therapy[J]. Oncogene, 2002, 21(35):5483-5495.
18. Steiner M, Clark B, Tang JZ, et al. 14-3-3σ mediates G2-M arrest produced by 5-aza-2'-deoxycytidine and possesses a tumor suppressor role in endometrial carcinoma cells[J]. Gynecol Oncol, 2012, 127(1):231-240.

West China Medical Journal

Protein Expression of RAS-association Domain Family 1A Gene and Its Significance in Patients with Vulvar Cancer

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