Study on the relationship between microsatellite instability status and clinicopathological characteristics of colorectal cancer patients

doi:10.3877/cma.j.issn.2095-3224.2021.02.004

Abstract

Abstract:

Objective

To identify the relationship between microsatellite instability(MSI) status and clinicopathological characteristics of colorectal cancer patients.

Methods

The clinicopathological data of 1 280 colorectal cancer patients from Jan 2015 to Dec 2019 were retrospectively analyzed. These patients had received radical resection for colorectal cancer in the Colorectal Surgery Department of the First Affiliated Hospital of Nanjing Medical University. Among these patients, there were 800 male and 480 female patients. The median age was 63 years (range 26~91 years). There were 337 right colon cancer patients, 398 left colon cancer patients and 545 rectal cancer patients. Microsatellite instability status was detected by polymerase chain reaction. The patients were divided into microsatellite instability high (MSI-H) and microsatellite stable/microsatellite instability low (MSS/MSI-L) groups. Patient characteristics, postoperative pathological examinations, MSI status were collected and analyzed. Count data were described as absolute numbers or percentages. Comparison of count data between groups was analyzed using the chi square test or Fisher's exact test. Rank sum test was used for ranked data. Measurement data with non-normal distribution were described as M (P25, P75), and comparison between groups was done using Mann-Whitney U Test.

Results

Among 1 280 colorectal cancer patients, 112(8.7%) patients were MSI-H, 79(6.2%) were MSI-L, and 1 089(85.1%) were MSS. Distinctive differences were found concerning preoperative blood serum level of CEA (χ²=6.943, P＜0.05), tumor localization (Z=-9.451, P＜0.001), TNM stage (Z=-2.108, P＜0.05), T stage (Z=-2.397, P＜0.05), N stage (Z=-3.892, P＜0.001), differentiation (χ²=6.663, P＜0.05), mucinous differentiation (χ²=78.833, P＜0.001), tumor size (χ²=39.656, P＜0.001), tumor deposits (χ²=8.759, P＜0.05), perineural invasion (χ²=10.238, P＜0.05), lymph node metastasis ratio (LNR) (χ²=5.880, P＜0.05), lymph node count (Z=-5.019, P＜0.001), positive lymph node count (Z=-3.667, P＜0.001) between MSI-H and MSS/MSI-L colorectal cancer patients. More patients were found with CEA＜4.7 ng/mL, right colon cancer, low TNM stage, high T stage, low N stage, poor differentiation, mucinous differentiation, tumor size ≥4 cm, no tumor deposits, no perineural invasion, low lymph node ratio, high lymph node count and low positive lymph node count in MSI-H patients.

Conclusion

Compared with MSS/MSI-L patients, MSI-H colorectal patients have distinctive clinicopathological features, with a mixture associated with both good and poor outcomes.

Key words: Colorectal neoplasms, Clinicopathological characteristics, Microsatellite status

Dongsheng Zhang, Yifei Feng, Yong Wang, Ziwei Xu, Junwei Tang, Yuanjian Huang, Chuan Zhang, Yueming Sun. Study on the relationship between microsatellite instability status and clinicopathological characteristics of colorectal cancer patients[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(02): 132-136.

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Figures/Tables 2

References 20

1	郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28.
2	Kawakami H, Zaanan A, Sinierope FA. Microsatellite instability testing and its role in the management of colorectal cancer[J]. Curr Treat Options Oncol, 2015, 16(7): 30.
3	Kazama Y, Watanabe T, Kanazawa T, et al. Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features[J]. J Clin Pathol, 2007, 60(6): 701-704.
4	中国临床肿瘤学会结直肠癌专家委员会, 中国抗癌协会大肠癌专业委员会遗传学组, 中国医师协会结直肠肿瘤专业委员会遗传专委会. 结直肠癌及其他相关实体瘤微卫星不稳定性检测中国专家共识[J]. 中华肿瘤杂志. 2019, 41(10): 734-741.
5	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.
6	王畅. 微卫星状态对结肠癌术后辅助化疗决策的影响[J/CD]. 中华结直肠疾病电子杂志, 2018, 7(3): 207-213.
7	Al-Sohaily S, Biankin A, Leong R, et al. Molecular pathways in colorectal cancer[J]. J Gastroenterol Hepatol, 2012, 27(9): 1423-1431.
8	Shin US, Cho SS, Moon SM, et al. Is microsatellite instability really a good prognostic factor of colorectal cancer?[J]. Ann Coloproctol, 2014, 30(1): 28-34.
9	Karahan B, Argon A, Yıldırım M, et al. Relationship between MLH-1, MSH-2, PMS-2, MSH-6 expression and clinicopathological features in colorectal cancer[J]. Int J Clin Exp Pathol, 2015, 8(4): 4044-4053.
10	陈美丽, 李琳, 禹立霞, 等. 微卫星状态与术后大肠癌患者的临床及病理特征相关性研究[J]. 中国肿瘤临床, 2018, 45(3): 131-136.
11	Kim YH, Min BH, Choi HK, et al. Sporadic colorectal carcinomas with low-level microsatellite instability in Korea: do they form a distinct subgroup with distinguished clinicopathological features?[J]. J Surg Oncol, 2009, 99(6): 351-355.
12	Gupta R, Sinha S, Paul RN. The impact of microsatellite stability status in colorectal cancer[J]. Curr Probl Cancer, 2018, 42(6): 548-559.
13	Kang S, Na Y, Joung SY, et al. The significance of microsatellite instability in colorectal cancer after controlling for clinicopathological factors[J]. Medicine (Baltimore), 2018, 97(9): e0019.
14	Belt EJ, te Velde EA, Krijgsman O, et al. High lymph node yield is related to microsatellite instability in colon cancer[J]. Ann Surg Oncol, 2012, 19(4): 1222-1230. URL
15	Berg M, Guriby M, Nordgård O, et al. Influence of microsatellite instability and KRAS and BRAF mutations on lymph node harvest in stage I-III colon cancers[J]. Mol Med, 2013, 19(1): 286-293.
16	Phillips SM, Banerjea A, Feakins R, et al. Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic[J]. Br J Surg, 2004, 91(4): 469-475.
17	Ogino S, Nosho K, Irahara N, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype[J]. Clin Cancer Res, 2009, 15(20): 6412-6420.
18	MurphyJohn, PocardMarc, JassJeremy R, et al. Number and size of lymph nodes recovered from dukes B rectal cancers: correlation with prognosis and histologic antitumor immune response [J]. Dis Colon Rectum, 2007, 50(10): 1526-1534. URL
19	Wirta EV, Seppälä T, Friman M, et al. Immunoscore in mismatch repair-proficient and -deficient colon cancer[J]. J Pathol Clin Res, 2017, 3(3): 203-213.
20	MacQuarrie E, Arnason T, Gruchy J, et al. Microsatellite instability status does not predict total lymph node or negative lymph node retrieval in stage III colon cancer[J]. Hum Pathol, 2012, 43(8): 1258-1264. URL

变量	MSS/MSI-L	MSI-H	χ²值	P值
性别			0.042	0.838
男	729（62.4）	71（63.4）
女	439（37.6）	41（36.6）
年龄（岁）			2.206	0.137
＜60	418（35.8）	48（42.9）
≥60	750（64.2）	64（57.1）
BMI（kg/m²）			0.600	0.439
＜24	639（54.7）	57（50.9）
≥24	529（45.3）	55（49.1）
CEA（ng/mL）			6.943	0.008
＜4.7	685（58.6）	80（71.4）
≥4.7	483（41.4）	32（28.6）
CA19-9（ng/mL）			0.032	0.857
＜39	1 015（86.9）	98（87.5）
≥39	153（13.1）	14（12.5）

变量	MSS/MSI-L	MSI-H	χ²值	P值
性别			0.042	0.838
男	729（62.4）	71（63.4）
女	439（37.6）	41（36.6）
年龄（岁）			2.206	0.137
＜60	418（35.8）	48（42.9）
≥60	750（64.2）	64（57.1）
BMI（kg/m²）			0.600	0.439
＜24	639（54.7）	57（50.9）
≥24	529（45.3）	55（49.1）
CEA（ng/mL）			6.943	0.008
＜4.7	685（58.6）	80（71.4）
≥4.7	483（41.4）	32（28.6）
CA19-9（ng/mL）			0.032	0.857
＜39	1 015（86.9）	98（87.5）
≥39	153（13.1）	14（12.5）

变量	MSS/MSI-L	MSI-H	检验值	P值
肿瘤部位			Z=-9.451	＜0.001
右半结肠	266（22.8）	71（63.4）
左半结肠	367（31.4）	31（27.7）
直肠	535（45.8）	10（8.9）
肿瘤TNM分期			Z=-2.108	0.035
Ⅰ	204（17.4）	11（9.80）
Ⅱ	565（48.4）	84（75.00）
Ⅲ	343（29.4）	16（14.30）
Ⅳ	56（4.8）	1（0.90）
肿瘤T分期			Z=-2.397	0.017
1	62（5.3）	2（1.8）
2	185（15.8）	9（8.0）
3	814（69.7）	90（80.4）
4a	101（8.6）	10（8.9）
4b	6（0.5）	1（0.9）
肿瘤N分期			Z=-3.892	＜0.001
0	781（66.9）	95（84.8）
1	255（21.8）	12（10.7）
2	132（11.3）	5（4.5）
肿瘤M分期			χ²=3.657	0.054
0	1 112（95.2）	111（99.1）
1	56（4.8）	1（0.9）
肿瘤分化			χ²=6.663	0.010
中高	816（69.9）	65（58.0）
低	352（30.1）	47（42.0）
印戒细胞			χ²=1.236	0.249
无	1 159（99.2）	110（98.2）
有	9（0.8）	2（1.8）
黏液成分			χ²=78.833	＜0.001
无	996（85.3）	58（51.8）
有	172（14.7）	54（48.2）
病理形态			χ²=2.052	0.152
溃疡	797（68.2）	69（61.6）
隆起	371（31.8）	43（38.4）
最大直径（cm）			χ²=39.656	＜0.001
＜4	503（43.1）	14（12.5）
≥4	665（56.9）	98（87.5）
癌结节			χ²=8.759	0.003
无	1 046（89.6）	110（98.2）
有	122（10.4）	2（1.8）
脉管侵犯			χ²=0.049	0.825
无	992（84.9）	96（85.7）
有	176（15.1）	16（14.3）
神经侵犯			χ²=10.238	0.001
无	985（84.3）	107（95.5）
有	183（15.7）	5（4.5）
LNR			χ²=5.880	0.015
＜0.25	1 073（91.9）	110（98.2）
≥0.25	95（8.1）	2（1.8）
淋巴结检出数（枚）	19（16,23）	22（18,30）	Z=-5.019	＜0.001
阳性淋巴结检出数（枚）	0（0,1）	0（0,0）	Z=-3.667	＜0.001

变量	MSS/MSI-L	MSI-H	检验值	P值
肿瘤部位			Z=-9.451	＜0.001
右半结肠	266（22.8）	71（63.4）
左半结肠	367（31.4）	31（27.7）
直肠	535（45.8）	10（8.9）
肿瘤TNM分期			Z=-2.108	0.035
Ⅰ	204（17.4）	11（9.80）
Ⅱ	565（48.4）	84（75.00）
Ⅲ	343（29.4）	16（14.30）
Ⅳ	56（4.8）	1（0.90）
肿瘤T分期			Z=-2.397	0.017
1	62（5.3）	2（1.8）
2	185（15.8）	9（8.0）
3	814（69.7）	90（80.4）
4a	101（8.6）	10（8.9）
4b	6（0.5）	1（0.9）
肿瘤N分期			Z=-3.892	＜0.001
0	781（66.9）	95（84.8）
1	255（21.8）	12（10.7）
2	132（11.3）	5（4.5）
肿瘤M分期			χ²=3.657	0.054
0	1 112（95.2）	111（99.1）
1	56（4.8）	1（0.9）
肿瘤分化			χ²=6.663	0.010
中高	816（69.9）	65（58.0）
低	352（30.1）	47（42.0）
印戒细胞			χ²=1.236	0.249
无	1 159（99.2）	110（98.2）
有	9（0.8）	2（1.8）
黏液成分			χ²=78.833	＜0.001
无	996（85.3）	58（51.8）
有	172（14.7）	54（48.2）
病理形态			χ²=2.052	0.152
溃疡	797（68.2）	69（61.6）
隆起	371（31.8）	43（38.4）
最大直径（cm）			χ²=39.656	＜0.001
＜4	503（43.1）	14（12.5）
≥4	665（56.9）	98（87.5）
癌结节			χ²=8.759	0.003
无	1 046（89.6）	110（98.2）
有	122（10.4）	2（1.8）
脉管侵犯			χ²=0.049	0.825
无	992（84.9）	96（85.7）
有	176（15.1）	16（14.3）
神经侵犯			χ²=10.238	0.001
无	985（84.3）	107（95.5）
有	183（15.7）	5（4.5）
LNR			χ²=5.880	0.015
＜0.25	1 073（91.9）	110（98.2）
≥0.25	95（8.1）	2（1.8）
淋巴结检出数（枚）	19（16,23）	22（18,30）	Z=-5.019	＜0.001
阳性淋巴结检出数（枚）	0（0,1）	0（0,0）	Z=-3.667	＜0.001

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