Effect of mismatch repair genes expression in right colon cancer on pathological characteristics

doi:10.16139/j.1007-9610.2021.01.013

Abstract

Abstract:

Objective To investigate the defect of expression of mismatch repair genes(MMR) including MLH1, MSH2, MSH6 and PMS2 in sporadic colon cancer, and analyze the expression of MMR related to pathological change of patients with right colon cancer. Methods The data of 206 patients with colon cancer including 116 cases with left colon cancer and 90 cases with right colon cancer in our hospital were collected from January 2015 to August 2020. The expression of MMR including MLH1, MSH2, MSH6 and PMS2 was detected by immunohistochemistry. The relation of defect in expression of MMR to pathological changes in colon cancer was analyzed. Results The rate of expression defect of MMR in patients with right colon cancer was higher than that in patients with left colon cancer. The expression defect of MMR was significantly related to tumor differentiation and neural invasion in patients with right colon cancer (P<0.05). Conclusions Higher rate of expression defect of MMR in patients with sporadic right colon cancer was present compared with the patients of left colon cancer. The patients of right colon cancer with expression defect of MMR have poorly pathological differentiated and are unprone to perineural invasion.

Key words: Mismatch repair gene, Pathology, Colon cancer

CLC Number:

R735.35

YAN Wanneng, MA Haijie, SHEN Chaomin. Effect of mismatch repair genes expression in right colon cancer on pathological characteristics[J]. Journal of Surgery Concepts & Practice, 2021, 26(01): 62-65.

Figures/Tables 3

References 20

[1]	Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality[J]. Gut, 2017, 66(4):683-691.
[2]	国家卫生计生委医政医管局, 中华医学会肿瘤学分会. 中国结直肠癌诊疗规范(2017年版)[J]. 中国实用外科杂志, 2018, 38(10):1089-1103. doi: 10.19538/j.cjps.issn1005-2208.2018.10.01
[3]	Bufill JA. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location[J]. Ann Intern Med, 1990, 113(10):779-788. pmid: 2240880
[4]	Nyström-Lahti M, Parsons R, Sistonen P, et al. Mismatch repair genes on chromosomes 2p and 3p account for a major share of hereditary nonpolyposis colorectal cancer families evaluable by linkage[J]. Am J Human Genetics, 1994, 55(4):659-665.
[5]	Iyer RR, Pluciennik A, Burdett V, et al. DNA mismatch repair: functions and mechanisms[J]. Chem Rev, 2006, 106(2):302-320.
[6]	Han Y, Peng Y, Fu Y, et al. MLH1 deficiency induces cetuximab resistance in colon cancer via Her-2/PI3K/AKT signaling[J]. Adv Sci (Weinh), 2020, 7(13):2000112.
[7]	Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer[J]. Nat Genet, 2006, 38(7):787-793. doi: 10.1038/ng1834 pmid: 16804544
[8]	Chang K, Taggart MW, Reyes-Uribe L, et al. Immunotherapy is active in MMR- deficient and MMR-proficient colon cancer[J]. Cancer Discov, 2020, 10(6):760.
[9]	Liu W, Zhang D, Tan SA, et al. Sigmoid colon adenocarcinoma with isolated loss of PMS2 presenting in a patient with synchronous prostate cancer with intact MMR: diagnosis and analysis of the family pedigree[J]. Anticancer Res, 2018, 38(8):4847-4852.
[10]	Nosho K, Irahara N, Shima K, et al. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample[J]. PloS One, 2008, 3(11):3698.
[11]	Li SKH, Martin A. Mismatch repair and colon cancer: mechanisms and therapies explored[J]. Trends Mol Med, 2016, 22(4):274-289.
[12]	Vasaikar S, Huang C, Wang X, et al. Clinical proteomic tumor analysis consortium. proteogenomic analysis of human colon cancer reveals new therapeutic opportunities[J]. Cell, 2019, 177(4):1035-1049. doi: S0092-8674(19)30292-2 pmid: 31031003
[13]	Fanelli GN, Dal Pozzo CA, Depetris I, et al. The heterogeneous clinical and pathological landscapes of metastatic Braf-mutated colorectal cancer[J]. Cancer Cell Int, 2020, 20:30.
[14]	Aaltonen LA, Peltomäki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal-cancer[J]. Science, 1993, 260(5109):812-816. doi: 10.1126/science.8484121 pmid: 8484121
[15]	Tauriello DVF, Palomo-Ponce S, Stork D, et al. TGF-β drives immune evasion in genetically reconstituted colon cancer metastasis[J]. Nature, 2018, 554(7693):538-543.
[16]	Zhang TM, Huang T, Wang RF. Cross talk of chromosome instability, CpG island methylator phenotype and mismatch repair in colorectal cancer[J]. Oncol Lett, 2018, 16(2):1736-1746.
[17]	Chung DC. Genetic testing and early onset colon cancer[J]. Gastroenterology, 2018, 154(4):788-789.
[18]	Calabrese P, Tsao JL, Yatabe Y, et al. Colorectal pretumor progression before and after loss of DNA mismatch repair[J]. Am J Pathol, 2004, 164(4):1447-1453. pmid: 15039232
[19]	王铁延, 陈修文, 李妞妞, 等. 316例结直肠癌错配修复蛋白检测及Lynch综合症初步筛查策略[J]. 诊断病理学杂志, 2017, 26(5):297-302.
[20]	张园园, 邹霜梅, 王振宁, 等. 26 280例结直肠癌患者MLH1和PMS2基因表达情况及临床病理特征的多中心回顾性研究[J]. 中华结直肠疾病电子杂志, 2019, 2(8):16-22.

组别	MMR缺失	MMR表达	MLH1缺失	MSH2缺失	MSH6缺失	PMS2缺失
右半结肠癌（n=90）	12（13.33）	78	9（10.00）	3（3.33）	3（3.33）	9（10.00）
左半结肠癌（n=116）	9（7.76）	107	6（5.17）	3（2.59）	3（2.59）	6（5.17）
合计	21（10.19）	185	15	6	6	15

项目	病例数（n=90）	MMR表达		χ²值	P值
项目	病例数（n=90）	缺失（n=12）	表达（n=78）	χ²值	P值
性别
男	40	5(41.67%)	35(44.87%)	0.043	0.835
女	50	7(58.33%)	43(55.13%)
年龄（岁）
>50	81	9(75.00%)	72(92.31%)	1.806	0.179
≤50	9	3(25.00%)	6(7.69%)
肿瘤分化
低	19	7(58.33%)	12(15.38%)	9.711	0.012^a)
中	65	5(41.67%)	60(76.92%)
高	1	0	1(1.28%)
黏液腺癌	5	0	5(6.41%)
神经浸润
否	68	12(100%)	56(71.79%)	-	0.034^a)
是	22	0	22(28.21%)
脉管浸润
否	65	9(77.30%)	56（71.79%）	0.000	1.000
是	25	3（22.70%）	22（28.21%）
淋巴转移
否	45	5（41.67%）	40（51.28%）	0.385	0.535
是	45	7（58.33%）	38（48.72%）
TNM分期
Ⅰ	12	1(8.33%)	11(14.10%)	0.354	0.838
Ⅱ	33	5(41.67%)	28(35.90%)
Ⅲ	45	6(50.00%)	39(50.00%)