Expressions of p53 and hMLH1 in Early Rectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YU Xinming , LIN Guole , XIAO Yi , WU Bin , QIU Huizhong.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;

Corresponding author：

Keywords：

Early rectal cancer; p53 gene; hMLH1 gene; Immunohistochemistry

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Objective To explore whether mutations of p53 gene and hMLH1 gene may be an early event of carcinogenesis in rectal cancer.
Methods The expressions of p53 and hMLH1 protein in 32 patients with early rectal cancer, 32 patients with rectal adenoma， and 30 patients with normal rectal mucosa were detected by PV-9000 immunohistochemical method between February 2003 and July 2009 in this hospital.
Results ① The positive expression rates of p53 protein were 0 (0/30), 59.38% (19/32), and 68.75% (22/32) in the normal rectal mucosa, rectal adenoma, and early rectal cancer, respectively. There was no difference between the rectal adenoma and early rectal cancer (P gt;0.05), but which were higer than that of the normal rectal mucosa (P lt;0.01). The negative expression rates of hMLH1 protein were 0 (0/30), 12.50% (4/32), and 50.00% (16/32) in the normal rectal mucosa, rectal adenoma, and early rectal cancer, respectively. The negative expression rate of hMLH1 protein in the early rectal cancer was significantly higher than that in the rectal adenoma or the normal rectal mucosa (P lt;0.01). ② The positive expression of p53 concomitant negative expression of hMLH1 in the rectal adenoma and early rectal cancer were 9.38% (3/32) and 37.50% (12/32), respectively, the difference was statistically significant (P=0.008). ③ In the early rectal cancer, the positive expression of p53 and the negative expression of hMLH1 were closely related to the degree of differentiation (P lt;0.05), but which weren’t related to the patient’s gender, age, tumor maximum diameter, depth of invasion or fecal occult blood (P gt;0.05). ④ The positive expression of p53 was closely related to higher adenoma hyperplasia (P=0.009), while not of negative expression of hMLH1 (P gt;0.05).
Conclusion Simultaneous mutations of p53 gene and hMLH1 gene may be an early event of carcinogenesis in rectal cancer.

Citation： YU Xinming,LIN Guole,XIAO Yi,WU Bin,QIU Huizhong.. Expressions of p53 and hMLH1 in Early Rectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(9): 889-893. doi: Copy

1.	中国抗癌协会大肠癌专业委员会腹腔镜外科学组, 中华医学会外科分会腹腔镜与内镜外科学组. 腹腔镜结肠直肠癌根治手术操作指南（2006版） [J]. 外科理论与实践, 2006; 11(5): 462464．.
2.	Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin, 2005; 55(2): 74108.
3.	Zhao DB, Wu YK, Shao YF, et al. Prognostic factors for 5year survival after local excision of rectal cancer [J]. World J Gastroenterol, 2009; 15(10): 12421245.
4.	宋恕平. 结直肠癌的内科治疗及进展 [J]．中华肿瘤防治杂志, 2006; 13（14）: 10411042.
5.	黄桂林, 吴毅平, 雷娜. 胰岛素样生长因子1在原发性结直肠癌中表达的研究 [J]. 中国普外基础与临床杂志， 2009; 16(9): 693697.
6.	徐徕, 林国乐, 肖毅, 等. 腹腔镜技术在中低位直肠癌中的应用 [J]. 中国现代手术学杂志, 2009; 13（5）: 387390.
7.	Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer [J]. Cancer Res, 1998; 58(22): 52485257.
8.	斯向东, 舒畅, 徐宾, 等. O6甲基鸟嘌呤-DNA甲基转移酶与P53蛋白在结直肠癌中的表达及其临床病理意义 [J]. 实用医学杂志, 2009; 25（24）: 41164118.
9.	Nunes BL, Jucá MJ, Gomes EG, et al. Metalloproteinase1, metalloproteinase7, and p53 immunoexpression and their correlation with clinicopathological prognostic factors in colorectal adenocarcinoma [J]. Int J Biol Markers, 2009; 24(3): 156164.
10.	宋枫, 高峰, 董亮, 等. p53和nm23在结直肠癌中的表达 [J]. 西北国防医学杂志, 2010; 31(1）: 1921.
11.	陈小贺, 孟文格, 孟繁杰, 等. 大肠癌组织中cyclin D1和p16及Rb的表达及其临床意义 [J]．中华肿瘤防治杂志，2006; 13(1): 3841．.
12.	单宝珍, 童强, 李梅, 等. 大肠癌发生中突变型P53与hMLH1表达的关系 [J]. 大连医科大学学报, 2009; 31(3): 270273.
13.	Chaksangchaichot P, Punyarit P, Petmitr S. Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer [J]. J Cancer Res Clin Oncol, 2007; 133(1): 6570．.
14.	Frayling IM. Methods of molecular analysis: mutation detection in solid tumours [J]. Mol Pathol, 2002; 55(2): 7379．.
15.	孟东, 杭剑萍, 王卫理．环氧化酶2和p53与大肠癌的临床病理研究 [J]．肿瘤研究与临床, 2006; 18(6): 383385．.
16.	董崇海, 曲玲, 赵清喜, 等. 散发性结直肠癌、腺瘤组织中hMLH1和突变型p53表达 [J]. 中国肿瘤, 2007; 16(2): 123126.
17.	Fox EJ, Leahy DT, Geraghty R, et al. Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6 methylguanine DNA methyltransferase in colorectal cancer [J]. J Mol Diagn, 2006; 8(1): 6875.
18.	Shia J, Ellis NA, Klimstra DS. The utility of immunohistochemical detection of DNA mismatch repair gene proteins [J]. Virchows Arch, 2004; 445(5): 431441.

1. 中国抗癌协会大肠癌专业委员会腹腔镜外科学组, 中华医学会外科分会腹腔镜与内镜外科学组. 腹腔镜结肠直肠癌根治手术操作指南（2006版） [J]. 外科理论与实践, 2006; 11(5): 462464．.
2. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin, 2005; 55(2): 74108.
3. Zhao DB, Wu YK, Shao YF, et al. Prognostic factors for 5year survival after local excision of rectal cancer [J]. World J Gastroenterol, 2009; 15(10): 12421245.
4. 宋恕平. 结直肠癌的内科治疗及进展 [J]．中华肿瘤防治杂志, 2006; 13（14）: 10411042.
5. 黄桂林, 吴毅平, 雷娜. 胰岛素样生长因子1在原发性结直肠癌中表达的研究 [J]. 中国普外基础与临床杂志， 2009; 16(9): 693697.
6. 徐徕, 林国乐, 肖毅, 等. 腹腔镜技术在中低位直肠癌中的应用 [J]. 中国现代手术学杂志, 2009; 13（5）: 387390.
7. Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer [J]. Cancer Res, 1998; 58(22): 52485257.
8. 斯向东, 舒畅, 徐宾, 等. O6甲基鸟嘌呤-DNA甲基转移酶与P53蛋白在结直肠癌中的表达及其临床病理意义 [J]. 实用医学杂志, 2009; 25（24）: 41164118.
9. Nunes BL, Jucá MJ, Gomes EG, et al. Metalloproteinase1, metalloproteinase7, and p53 immunoexpression and their correlation with clinicopathological prognostic factors in colorectal adenocarcinoma [J]. Int J Biol Markers, 2009; 24(3): 156164.
10. 宋枫, 高峰, 董亮, 等. p53和nm23在结直肠癌中的表达 [J]. 西北国防医学杂志, 2010; 31(1）: 1921.
11. 陈小贺, 孟文格, 孟繁杰, 等. 大肠癌组织中cyclin D1和p16及Rb的表达及其临床意义 [J]．中华肿瘤防治杂志，2006; 13(1): 3841．.
12. 单宝珍, 童强, 李梅, 等. 大肠癌发生中突变型P53与hMLH1表达的关系 [J]. 大连医科大学学报, 2009; 31(3): 270273.
13. Chaksangchaichot P, Punyarit P, Petmitr S. Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer [J]. J Cancer Res Clin Oncol, 2007; 133(1): 6570．.
14. Frayling IM. Methods of molecular analysis: mutation detection in solid tumours [J]. Mol Pathol, 2002; 55(2): 7379．.
15. 孟东, 杭剑萍, 王卫理．环氧化酶2和p53与大肠癌的临床病理研究 [J]．肿瘤研究与临床, 2006; 18(6): 383385．.
16. 董崇海, 曲玲, 赵清喜, 等. 散发性结直肠癌、腺瘤组织中hMLH1和突变型p53表达 [J]. 中国肿瘤, 2007; 16(2): 123126.
17. Fox EJ, Leahy DT, Geraghty R, et al. Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6 methylguanine DNA methyltransferase in colorectal cancer [J]. J Mol Diagn, 2006; 8(1): 6875.
18. Shia J, Ellis NA, Klimstra DS. The utility of immunohistochemical detection of DNA mismatch repair gene proteins [J]. Virchows Arch, 2004; 445(5): 431441.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of p53 and hMLH1 in Early Rectal Cancer

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