MSI状态与Ⅱ期、Ⅳ期结肠癌患者预后及其临床病理特征的相关性分析及思考

doi:10.3877/cma.j.issn.1674-3946.2019.03.022

目的

分析微卫星不稳定(MSI)状态与Ⅱ期、Ⅳ期结肠癌患者预后及其临床病理特征的相关性分析，探讨结肠癌患者病理分期及预后的评估思路。

方法

将2010年3月至2017年5月收治的271例结肠癌患者纳入前瞻性研究。按照患者MSI状态，将其分别纳入高频MSI组、低频MSI组以及微卫星稳定(MSS)组，采用SPSS 18.0进行分析，各组患者生存情况及临床病理特征以(例/%)表示，采用χ²检验；总生存期以(±s)表示，采用t检验；影响因素分析使用多因素Logistic回归模型。以P<0.05为差异有统计学意义。

结果

271例患者中，108例为高频MSI，86例为低频MSI，77例为MSS；MSI者占比为71.6%(194/271)。高频MSI患者总生存期为(26.2±3.8)个月，高于低频MSI组的(18.2±2.7)个月及MSS组的(17.6±2.6)个月，差异有统计学意义(P<0.05)。高频MSI组年龄、肿瘤部位、病理分型与低频MSI组、MSS组比较，差异有统计学意义(P<0.05)。多因素Logistic回归分析示，以随访期间死亡为因变量，年龄<65岁、高频MSI为保护因素，淋巴结转移为影响患者预后的独立危险因素(P<0.05)。

结论

Ⅱ期、Ⅳ期结肠癌患者中MSI者占比较高，高频MSI者有着特殊临床病理特征，包括年龄较低、肿瘤部位以右半结肠为主、病理分型以粘液腺癌为主等，且该类患者预后较为理想。

关键词: 结肠肿瘤, 微卫星不稳定性, 病理学，临床, 预后

Objective

To analyze the correlation of Microsatellite instability (MSI) status, clinicopathological features and prognosis of patients with II and IV stage colon cancer, therefore to predict pathological staging and prognosis of patients with colon cancers.

Methods

A total of 271 patients with colon cancer in our hospital from March 2010-May 2017 were enrolled into this prospective study. According to MSI status, patients were divided into high frequency MSI group, low frequency MSI group and the microsatellite stability (Microsatellite stability, MSS) group. Statistical analysis were performed by using SPSS18.0 software. Total survival time were expressed as mean±standard deviation, and were examined by t-test. The survival and clinicopathological characteristics of patients in each group were expressed as percentage (%), and was examined by chi-square test. The influencing factors were analyzed by multivariate Logistic regression model. A P value <0.05 was considered as significant difference.

Results

Among 271 patients, 108 cases were high frequency MSI, 86 cases were low-frequency MSI, while 77 cases were MSS, with MSI of 71.6%(194/271). Total survival time of (26.2±3.8) months in high frequency MSI group were, higher than (18.2±2.7) months and (17.6±2.6) months in low frequency MSI group and in MSS group respectively, with significant difference (P<0.05). There were significant differences in terms of age, tumor location and pathological type, between high frequency MSI group, low-frequency MSI group and MSS group (P<0.05). Multiple factor Logistic regression analysis showed that the death was a dependent variable during the follow-up period, while the age < 65 years and high frequency MSI were protective factors, and lymph node metastasis was an independent risk factor affecting the prognosis of patients (P<0.05).

Conclusion

There were high incidence of MSI in patients with stage II and IV colon cancer.Patients with high frequency MSI exhibit clinicopathological features, including young age, tumor location in right hemicolon and mainly of adenocarcinoma, importantly with pretty good prognosis.

Key words: Colonic neoplasms, Microsatellite instability, Pathology, clinical, Prognosis

图1 271例结肠癌患者高频MSI、低频MSI与MSS患者的生存曲线[MSI：微卫星不稳定；MSI－H：高频MSI；MSI－L：低频MSI；MSS：微卫星稳定]

表1 271例结肠癌患者不同MSI状态者临床病理特征比较[例(%)]

临床病理特征		高频MSI组(n＝108)	低频MSI组(n＝86)	MSS组(n＝77)	P值
年龄(岁)		?	?	?	?
?	<65	32(29.6)	24(27.9)^a	15(19.5)^a	<0.05
?	≥65	76(70.4)	62(72.1)	62(80.5)	<0.05
性别		?	?	?	?
?	男	65(60.2)	50(58.1)	49(63.6)	>0.05
?	女	43(39.8)	36(41.9)	28(36.4)	>0.05
肿瘤部位		?	?	?	?
左侧结肠		41(38.0)	50(58.1)^a	47(61.0)^a	<0.05
?	右半结肠	67(62.0)	36(41.9)	30(39.0)	<0.05
病理分型		?	?	?	?
?	高分化腺癌	10(9.3)	18(20.9)	8(10.4)	<0.05
?	中分化腺癌	65(60.2)	56(65.1)	62(80.5)
?	低分化腺癌	15(13.9)	8(9.3)	6(7.8)
?	粘液腺癌	18(16.7)	4(4.7)^a	1(1.3)^a
临床分期		?	?	?	?
?	Ⅱ期	67(62.0)	50(58.1)	44(57.1)	>0.05
?	Ⅳ期	41(38.0)	36(41.9)	33(42.9)	>0.05
淋巴结转移		?	?	?	?
?	有	31(28.7)	28(32.6)	27(35.1)	>0.05
?	无	77(71.3)	58(67.4)	50(64.9)	>0.05
浸润深度		?	?	?	?
?	浆膜浸润	48(44.4)	39(45.4)	17(22.0)	>0.05
?	浆膜未浸润	60(55.6)	47(54.6)	60(78.0)	>0.05

表1 271例结肠癌患者不同MSI状态者临床病理特征比较[例(%)]

临床病理特征		高频MSI组(n＝108)	低频MSI组(n＝86)	MSS组(n＝77)	P值
年龄(岁)		?	?	?	?
?	<65	32(29.6)	24(27.9)^a	15(19.5)^a	<0.05
?	≥65	76(70.4)	62(72.1)	62(80.5)	<0.05
性别		?	?	?	?
?	男	65(60.2)	50(58.1)	49(63.6)	>0.05
?	女	43(39.8)	36(41.9)	28(36.4)	>0.05
肿瘤部位		?	?	?	?
左侧结肠		41(38.0)	50(58.1)^a	47(61.0)^a	<0.05
?	右半结肠	67(62.0)	36(41.9)	30(39.0)	<0.05
病理分型		?	?	?	?
?	高分化腺癌	10(9.3)	18(20.9)	8(10.4)	<0.05
?	中分化腺癌	65(60.2)	56(65.1)	62(80.5)
?	低分化腺癌	15(13.9)	8(9.3)	6(7.8)
?	粘液腺癌	18(16.7)	4(4.7)^a	1(1.3)^a
临床分期		?	?	?	?
?	Ⅱ期	67(62.0)	50(58.1)	44(57.1)	>0.05
?	Ⅳ期	41(38.0)	36(41.9)	33(42.9)	>0.05
淋巴结转移		?	?	?	?
?	有	31(28.7)	28(32.6)	27(35.1)	>0.05
?	无	77(71.3)	58(67.4)	50(64.9)	>0.05
浸润深度		?	?	?	?
?	浆膜浸润	48(44.4)	39(45.4)	17(22.0)	>0.05
?	浆膜未浸润	60(55.6)	47(54.6)	60(78.0)	>0.05

表2 影响271例结肠癌患者预后的多因素回归分析结果

影响因素	β	SE(β)	Waldχ²值	P值	OR	95% CI
年龄<65岁	－0.625	0.136	21.119	0.000	0.535	0.410～0.699
男性	0.319	0.358	0.794	0.057	1.376	0.682～2.775
肿瘤位于左侧结肠	0.252	0.184	1.876	0.063	1.287	0.897～1.845
粘液腺癌	－0.525	0.491	1.143	0.071	0.592	0.226～1.549
临床分期Ⅱ期	－0.241	0.408	0.349	0.049	0.786	0.353～1.748
淋巴结转移	0.523	0.186	7.906	0.000	1.687	1.172～2.429
浆膜浸润	0.424	0.138	9.440	0.054	1.528	1.166～2.003
高频MSI	－1.326	0.581	5.209	0.000	0.266	0.085～0.829

表2 影响271例结肠癌患者预后的多因素回归分析结果

影响因素	β	SE(β)	Waldχ²值	P值	OR	95% CI
年龄<65岁	－0.625	0.136	21.119	0.000	0.535	0.410～0.699
男性	0.319	0.358	0.794	0.057	1.376	0.682～2.775
肿瘤位于左侧结肠	0.252	0.184	1.876	0.063	1.287	0.897～1.845
粘液腺癌	－0.525	0.491	1.143	0.071	0.592	0.226～1.549
临床分期Ⅱ期	－0.241	0.408	0.349	0.049	0.786	0.353～1.748
淋巴结转移	0.523	0.186	7.906	0.000	1.687	1.172～2.429
浆膜浸润	0.424	0.138	9.440	0.054	1.528	1.166～2.003
高频MSI	－1.326	0.581	5.209	0.000	0.266	0.085～0.829

[1]	Mlecnik B, Bindea G, Angell HK, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability[J]. Immunity, 2016, 44(3): 698-711.
[2]	Kawakami H, Zaanan A, Sinicrope FA.Microsatellite instability testing and its role in the management of colorectal cancer[J]. Curr Treat Options Oncol, 2015, 16(7): 30-30.
[3]	Hechtman JF, Middha S, Stadler ZK, et al.Universal screening for microsatellite instability in colorectal cancer in the clinical genomics era: new recommendations, methods, and considerations[J]. Fam Cancer, 2017, 16(4): 525-529.
[4]	秦云，梁莉萍，郑兴征，等．免疫组织化学法检测结直肠癌四种DNA错配修复蛋白表达缺失对判断肿瘤微卫星状态的价值[J]．中华病理学杂志，2015，44(10)：704-708.
[5]	Overman MJ, McDermott R, Leach JL, et al.Nivolumab in patients with metastatic DNA mismatch repair－deficient or microsatellite instability－high colorectal cancer (CheckMate 142): an open－label, multicentre, phase 2 study[J]. Lancet Oncol, 2017, 18(9): 1182-1191.
[6]	Irabor DO, Oluwasola OA, Ogunbiyi OJ, et al.Microsatellite Instability Is Common in Colorectal Cancer in Native Nigerians[J]. Anticancer Res, 2017, 37(5): 2649-2654.
[7]	赵喜连，郗彦凤，白文启，等．错配修复蛋白和p53蛋白表达与结直肠癌的临床病理关系及其相关性[J]．临床与实验病理学杂志，2016, 32(4): 370-374，379.
[8]	Carethers JM, Koi M, Tseng－Rogenski SS. EMAST is a form of microsatellite instability that is initiated by inflammation and modulates colorectal cancer progression[J]. Genes, 2015, 6(2): 185-205.
[9]	Sinicrope FA. The role of microsatellite instability testing in management of colorectal cancer[J]. Clin Adv Hematol Oncol, 2016, 14(7): 476-479.
[10]	徐星宇．结直肠癌中RNF43基因突变的病理意义[D]．浙江：浙江大学，2016：1-59.
[11]	Sepp？l? TT, B？hm JP, Friman M, et al. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer[J]. Br J Cancer, 2015, 112(12): 1966-1975.
[12]	余仙，赵和照．MMR/MSI在Ⅱ/Ⅲ期结直肠癌辅助化疗中的应用进展[J]．中国肿瘤，2016，25(12)：994-998.
[13]	李惠，孙怡，刘春样，等. MLH1、MSH2、MSH6和PMS2蛋白在结直肠癌中的表达及在Lynch综合征筛查中的意义[J]．临床与实验病理学杂志，2017，33(4)：360-364.
[14]	Llosa NJ, Cruise M, Tam A, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter－inhibitory checkpoints[J]. Cancer Discov, 2015, 5(1): 43-51.
[15]	Xiao Y, Freeman GJ. The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy[J]. Cancer Discov, 2015, 5(1): 16-18.
[16]	付极，林国乐．分子诊断技术在结直肠癌个体化精准治疗中的应用[J]．中华胃肠外科杂志，2016，19(1)：22-26.
[17]	Setaffy L, Langner C. Microsatellite instability in colorectal cancer: clinicopathological significance[J]. Pol J Pathol, 2015, 66(3): 203-218.
[18]	Gagnière J, Bonnin V, Jarrousse AS, et al. Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer[J]. Clin Sci, 2017, 131(6): 471-485.

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Correlation between MSI status, clinicopathological features and prognosis of patients with stage Ⅱ and Ⅳ colon cancer

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Correlation between MSI status, clinicopathological features and prognosis of patients with stage Ⅱ and Ⅳ colon cancer