切换至 "中华医学电子期刊资源库"
高级检索
中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (03) : 185 -192. doi: 10.3877/cma.j.issn.1674-0793.2021.03.005

所属专题： 文献；

论著

Ⅱ期结直肠癌中微卫星状态与差分化细胞群的关系及其对预后的影响
陈振伟1, 邱敏1, 姚秀娟2, 胡毕文1, 曹晨曦1,†(), 于亚威2   
  1. 1. 314000　嘉兴学院附属第二医院肛肠外科
    2. 314000　嘉兴学院附属第二医院病理科
  • 收稿日期:2020-10-12 出版日期:2021-06-01
  • 通信作者: 曹晨曦
  • 基金资助:
    浙江省医药卫生计划项目(2021KY354); 嘉兴市科技局项目(2019AD32254，2018AY32002)

Correlation between microsatellite status and poorly differentiated clusters and their prognostic value in stageⅡ colorectal cancer

Zhenwei Chen1, Min Qiu1, Xiujuan Yao2, Biwen Hu1, Chenxi Cao1,†(), Yawei Yu2   

  1. 1. Department of Anorectal Surgery, the Second Affiliated Hospital of Jiaxing College, Jiaxing 314000, China
    2. Department of Pathology, the Second Affiliated Hospital of Jiaxing College, Jiaxing 314000, China
  • Received:2020-10-12 Published:2021-06-01
  • Corresponding author: Chenxi Cao
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

陈振伟, 邱敏, 姚秀娟, 胡毕文, 曹晨曦, 于亚威. Ⅱ期结直肠癌中微卫星状态与差分化细胞群的关系及其对预后的影响[J/OL]. 中华普通外科学文献(电子版), 2021, 15(03): 185-192.

Zhenwei Chen, Min Qiu, Xiujuan Yao, Biwen Hu, Chenxi Cao, Yawei Yu. Correlation between microsatellite status and poorly differentiated clusters and their prognostic value in stageⅡ colorectal cancer[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(03): 185-192.

目的

探讨Ⅱ期结直肠癌中微卫星状态（MS）与差分化细胞群（PDC）之间的相关性及其对患者预后的影响，为术后辅助治疗提供参考。

方法

回顾性收集2014年12月至2017年12月在嘉兴学院附属第二医院行根治性手术的311例Ⅱ期结直肠癌患者的临床病理资料和随访结果，分析MS、PDC之间的相关性以及两者与其他临床病理特征之间的关系。采用Kaplan-Meier法绘制生存曲线，比较不同的MS和PDC状态对患者无病生存期（DFS）的影响。多因素Cox回归分析预后的影响因素。

结果

311例中微卫星稳定（MSS）252例，微卫星不稳定（MSI）59例；按PDC二分类法，PDC阳性（PDC+）171例，PDC阴性（PDC-）140例；按PDC三分级法，G1 210例，G2 57例，G3 44例。MS与PDC无明确相关性。MSS和MSI患者的中位DFS，总体比较和PDC-亚组中比较差异无统计学意义（P=0.232、0.589），但在PDC+亚组中差异有统计学意义（P=0.027）；PDC+和PDC-患者的中位DFS，总体比较和MSS亚组中比较差异有统计学意义（P=0.001、<0.001），而在MSI亚组中差异无统计学意义（P=0.935）；G1、G2和G3患者的中位DFS，无论是总体比较还是MSS亚组、MSI亚组中比较，差异均无统计学意义（P=0.246、0.371、0.498）。基于PDC和MS的联合分组中PDC+MSI组、PDC-MSI组、PDC+MSS组和PDC-MSS组的中位DFS差异有统计学意义（P=0.001），其中PDC+MSS组的DFS明显小于其他三组。多因素分析显示，PDC+MSS是影响DFS的独立预后因素（HR=2.670，95% CI：1.537~4.637，P<0.001）。

结论

Ⅱ期CRC中MS与PDC无明确相关性，但二者共同影响患者的预后。MSS和MSI患者的生存差异主要见于PDC+的患者，而在PDC-的患者中无明显差异；PDC+和PDC-患者的生存差异主要见于MSS的患者，而在MSI的患者中无明显差异。对于MSS且PDC+的患者，应予以积极的辅助治疗。对于Ⅱ期CRC来说，PDC的二分类法比三分级法更有临床价值，建议将PDC+纳入复发危险因素。

关键词: 微卫星状态, 差分化细胞群, 结直肠肿瘤, 无病生存期
Objective

To investigate the correlation between microsatellite status (MS) and poorly differentiated clusters (PDC) in stage Ⅱ colorectal cancer and their influences on prognosis, and to provide reference for postoperative adjuvant therapy.

Methods

The clinical, pathological and survival data of 311 patients with stage colorectal cancer who underwent radical surgery in the Second Affiliated Hospital of Jiaxing College from December 2014 to December 2017 were collected retrospectively. The correlation among MS, PDC and other clinicopathologic parameters was analyzed. After follow-up, the survival curves were plotted with Kaplan-Meier method to compare disease free survival (DFS) between different MS and PDC status. The prognostic factors were analyzed by multivariate Cox regression.

Results

Among the 311 patients, there were 252 microsatellite stability (MSS) and 59 microsatellite instability (MSI) cases. According to two classification method, the number of PDC positive (PDC+) and PDC negative (PDC-)were 171 and 140 cases, respectively. According to three grade method, the number of PDC G1, G2 and G3 were 210, 57 and 44 cases, respectively. There was no clear correlation between MS and PDC. There was no significant difference in median DFS between MSS and MSI patients in overall comparison or PDC-subgroup (P=0.232, 0.589), but with a statistically significant difference in PDC+ subgroup (P=0.027). There were significant differences in median DFS between PDC+ and PDC-patients in overall comparison and MSS subgroup (P<0.01), but without significant difference in MSI subgroup (P=0.935). There was no significant difference in the median DFS of G1, G2 and G3 patients, either in overall comparison or in MSS subgroup and MSI subgroup (P=0.246, 0.371, 0.498). Joint grouping based on PDC and MS, there was significant difference in median DFS of PDC+MSI, PDC-MSI, PDC+MSS and PDC-MSS groups (P=0.001), and PDC+MSS group had a worse survival than the other groups. Multivariate Cox regression analysis showed that PDC+MSS was an independent prognostic factor for DFS (HR=2.670, 95% CI: 1.537-4.637, P<0.001).

Conclusions

There is no definite correlation between MS and PDC in stage Ⅱ CRC, but both of them affect the prognosis of patients. Survival difference between MSS and MSI is mainly found in PDC+ patients, but not in PDC-patients. Survival difference between PDC+ and PDC-patients is mainly found in MSS patients, but not in MSI patients. For patients with MSS and PDC+, active adjuvant therapy should be given. For stage Ⅱ CRC, two classification method of PDC is more clinically valuable than three grade method, and PDC+ may be considered as a risk factor for recurrence.

Key words: Microsatellite status, Poorly differentiated clusters, Colorectal neoplasms, Disesse free survival
表1 不同微卫星状态的Ⅱ期结直肠癌患者临床病理特征比较
项目 例数 微卫星状态 统计值 P值
MSS(252例) MSI(59例)
性别       1.426 0.232
  男 195 162(64.29) 33(55.93)    
  女 116 90(35.71) 26(44.07)    
年龄(岁)a   63.26±12.26 63.69±13.64 0.241 0.810
肿瘤位置       5.401 0.020
  左半结直肠 218 184(73.08) 34(57.63)    
  右半结直肠 93 68(26.98) 25(42.37)    
组织学分级       12.919 0.005
  1级 6 5(1.98) 1(1.69)    
  2级 207 179(71.03) 28(47.46)    
  3级 87 61(24.21) 26(44.07)    
  4级 11 7(2.78) 4(6.78)    
T分期       0.187 0.665
  T3 166 136(53.97) 30(50.85)    
  T4 145 116(46.03) 29(49.15)    
脉管侵犯       0.037 0.848
  有 50 41(16.27) 9(15.25)    
  无 261 211(83.73) 50(84.75)    
神经侵犯       <0.001 0.993
  有 21 17(6.75) 4(6.78)    
  无 290 235(93.25) 55(93.22)    
PDC二分类法       0.026 0.871
  PDC+ 171 138(54.76) 33(55.93)    
  PDC- 140 114(45.24) 26(44.07)    
PDC三分级法       0.836 0.658
  G1 210 171(67.86) 39(66.10)    
  G2 57 44(17.46) 13(22.03)    
  G3 44 37(14.68) 7(11.87)    
图1 差分化细胞群（PDC）的苏木精-伊红染色病理图片　A为PDC-（200×）；B为PDC G1（200×）；C为PDC G2（200×）；D为PDC G3（400×）
表2 不同PDC状态患者之间临床病理特征比较
项目 PDC二分类法 统计值 P值 PDC三分级法 统计值 P值
PDC+(171例) PDC-(140例) G1(210例) G2(57例) G3(44例)
性别     0.176 0.724       0.041 0.980
  男 109(63.74) 86(61.43)     132(62.86) 36(63.16) 27(61.36)    
  女 62(36.26) 54(38.57)     78(37.14) 21(36.84) 17(38.64)    
年龄(岁) 63.42±12.76 63.24±12.25 0.125a 0.901 63.39±12.18 64.19±12.45 62.00±14.25 0.385b 0.681
肿瘤位置     2.921 0.087       0.093 0.954
  左半结直肠 113(66.08) 105(75.00)     148(70.48) 39(68.42) 31(70.45)    
  右半结直肠 58(33.92) 35(25.00)     62(29.52) 18(31.58) 13(29.55)    
组织学分级     4.402 0.221       10.604 0.101
  1级 2(1.17) 4(2.86)     6(2.86) 0(0) 0(0)    
  2级 112(65.50) 95(67.85)     143(68.10) 33(57.90) 31(70.45)    
  3级 48(28.07) 39(27.86)     57(27.14) 19(33.33) 11(25.00)    
  4级 9(5.26) 2(1.43)     4(1.90) 5(8.77) 2(4.55)    
T分期     4.489 0.040       2.250 0.325
  T3 82(47.95) 84(60.00)     118(56.19) 26(45.61) 22(50.00)    
  T4 89(52.05) 56(40.00)     92(43.81) 31(54.39) 22(50.00)    
脉管侵犯     26.238 <0.001       13.044 0.001
  有 44(25.73) 6(4.29)     23(10.95) 14(24.56) 13(29.55)    
  无 127(74.27) 134(95.71)     187(89.05) 43(75.44) 31(70.45)    
神经侵犯     11.462 0.001       1.792 0.408
  有 19(11.11) 2(1.43)     13(6.19) 3(5.26) 5(11.36)    
  无 152(88.89) 138(98.57)     197(93.81) 54(94.74) 39(88.64)    
图2 微卫星状态与Ⅱ期结直肠癌预后的关系　A为微卫星不稳定（MSI）与微卫星稳定（MSS）患者的生存曲线比较；B为差分化细胞群（PDC）+亚组中MSS和MSI患者的生存曲线比较；C为PDC-亚组中MSS和MSI患者的生存曲线比较；风险人数，即存在复发风险的人数，为每组中在术后0、20、40、60个月时仍无病生存的病例数
图3 差分化细胞群（PDC）二分类法与Ⅱ期结直肠癌预后的关系　A为PDC+与PDC-患者的生存曲线比较；B为微卫星稳定（MSS）亚组中PDC+和PDC-患者的生存曲线比较；C为微卫星不稳定（MSI）亚组中PDC+和PDC-患者的生存曲线比较；风险人数，即存在复发风险的人数，为每组在术后0、20、40、60个月时仍无病生存的病例数
图4 差分化细胞群（PDC）三分级法与Ⅱ期结直肠癌预后的关系　A为PDC G1、G2和G3患者的生存曲线比较；B为微卫星稳定（MSS）亚组中PDC G1、G2和G3患者的生存曲线比较；C为微卫星不稳定（MSI）亚组中PDC G1、G2和G3患者的生存曲线比较；风险人数，即存在复发风险的人数，为每组在术后0、20、40、60个月时仍无病生存的病例数
图5 基于差分化细胞群（PDC）和微卫星状态（MS）的联合分组与Ⅱ期结直肠癌预后的关系　PDC+MSI组、PDC-MSI组、PDC+MSS组和PDC-MSS组的生存曲线比较；风险人数，即存在复发风险的人数，为每组在术后0、20、40、60个月时仍无病生存的病例数
[1]
Karlberg M, Stenstedt K, Hallström M, et al. Tumor budding versus mismatch repair status in colorectal cancer - an exploratory analysis[J]. Anticancer Res, 2018, 38(8): 4713-4721.
[2]
刘方奇，蔡三军. 结直肠癌围手术期辅助与新辅助治疗[J]. 中华胃肠外科杂志, 2019, 22(4): 315-320.
[3]
National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Colon Cancer (NCCN Guidelines®) (2018 Version 4) [EB/OL]. (2018-10-19)[2019-01-22].

URL    
[4]
Ueno H, Kajiwara Y, Shimazaki H, et al. New criteria for histologic grading of colorectal cancer[J]. Am J Surg Pathol, 2012, 36(2):193-201.
[5]
Romiti A, Roberto M, Marchetti P, et al. Study of histopathologic parameters to define the prognosis of stage Ⅱ colon cancer[J]. Int J Colorectal Dis, 2019, 34(5): 905-913.
[6]
Lee V, Chan KF. Tumor budding and poorly-differentiated cluster in prognostication in stage colon cancer[J]. Pathol Res Pract, 2018, 214(3): 402-407.
[7]
Barresi V, Branca G, Ieni A, et al. Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer[J]. Virchows Arch, 2014, 464(6): 655-662.
[8]
Barresi V, Bonetti LR, Ieni A, et al. Histologic grading based on counting poorly differentiated clusters in preoperative biopsy predicts nodal involvement and pTNM stage in colorectal cancer patients[J]. Hum Pathol, 2014, 45(2): 268-275.
[9]
Machado I, Valera-Alberni M, Martínez de Juan F, et al. Histological factors predicting loco-regional lymph node metastasis in early invasive colorectal adenocarcinoma pT1[J]. Gastroenterol Hepatol, 2016, 39(1): 1-8.
[10]
Barresi V, Bonetti LR. Correlation between microsatellite instability status and grading assessed by the counting of poorly differentiated clusters in colorectal cancer[J]. Hum Pathol, 2015, 46(7): 1063.
[11]
Kim JW, Shin MK, Kim BC. Clinicopathologic impacts of poorly differentiated cluster-based grading system in colorectal carcinoma[J]. J Korean Med Sci, 2015, 30(1): 16-23.
[12]
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]. 实用肿瘤杂志, 2019, 34(5): 381-389.
[13]
中华人民共和国卫生和计划生育委员会医政医管局，中华医学会肿瘤学分会. 中国结直肠癌诊疗规范(2017年版)[J]. 中华外科杂志, 2018, 56(4): 241-258.
[14]
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.
[15]
Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer[J]. N Engl J Med, 2003, 349(3): 247-257.
[16]
石雪迎，郑杰. 系统筛查微卫星不稳定性结直肠癌的意义和策略[J]. 中华病理学杂志, 2015, 44(1): 9-14.
[17]
Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer[J]. J Clin Oncol, 2010, 28(20): 3219-3226.
[18]
Merok MA, Ahlquist T, Røyrvik EC, et al. Microsatellite instability has a positive prognostic impact on stage Ⅱ colorectal cancer after complete resection: results from a large, consecutive Norwegian series[J]. Ann Oncol, 2013, 24(5): 1274-1282.
[19]
Tajima Y, Shimada Y, Kameyama H, et al. Association between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage Ⅲ colorectal cancer[J]. Jpn J Clin Oncol, 2017, 47(4): 313-320.
[20]
杨路路，苟思琪，王劲松, 等. 结直肠腺癌中差分化细胞群的临床病理意义[J]. 中华病理学杂志, 2019, 48(4): 276-281.
[21]
Fonseca GM, de Mello ES, Faraj SF, et al. Prognostic significance of poorly differentiated clusters and tumor budding in colorectal liver metastases[J]. J Surg Oncol, 2018, 117(7): 1364-1375.
[22]
Ryan É, Khaw YL, Creavin B, et al. Tumor budding and PDC grade are stage independent predictors of clinical outcome in mismatch repair deficient colorectal cancer[J]. Am J Surg Pathol, 2018, 42(1): 60-68.
[23]
Kim JW, Shin MK, Kim BC. Clinicopathologic impacts of poorly differentiated cluster-based grading system in colorectal carcinoma[J]. J Korean Med Sci, 2015, 30(1): 16-23.
[1] 罗青杉, 梅海涛, 郝家领, 蔡锦锋, 周润楷, 温玉刚. 连接蛋白43通过调控细胞周期抑制结直肠癌的增殖机制研究[J/OL]. 中华普通外科学文献(电子版), 2024, 18(05): 344-349.
[2] 徐逸男. 不同术式治疗梗阻性左半结直肠癌的疗效观察[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 72-75.
[3] 韩加刚, 王振军. 梗阻性左半结肠癌的治疗策略[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 450-458.
[4] 梁轩豪, 李小荣, 李亮, 林昌伟. 肠梗阻支架置入术联合新辅助化疗治疗结直肠癌急性肠梗阻的疗效及其预后的Meta 分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 472-482.
[5] 严虹霞, 王晓娟, 张毅勋. 2 型糖尿病对结直肠癌患者肿瘤标记物、临床病理及预后的影响[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 483-487.
[6] 赵磊, 刘文志, 林峰, 于剑, 孙铭骏, 崔佑刚, 张旭, 衣宇鹏, 于宝胜, 冯宁. 深部热疗在改善结直肠癌术后辅助化疗副反应及生活质量中的作用研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 488-493.
[7] 黄海洋, 邝永龙, 陈嘉胜. 基层医院结直肠肿瘤经自然腔道取标本手术30 例分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 510-518.
[8] 任佳琪, 刁德昌, 何自衍, 张雪阳, 唐新, 李文娟, 李洪明, 卢新泉, 易小江. 网膜融合线导向的脾曲游离技术在左半结肠癌根治术中的应用[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 362-367.
[9] 张迪, 王春霞, 张学东, 李发馨, 庞淅文, 陈一锋, 张维胜, 王涛. 梗阻性左半结直肠癌自膨式金属支架置入后行腹腔镜手术与开腹手术的短期临床疗效比较[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 375-380.
[10] 张蔚林, 王哲学, 白峻阁, 黄忠诚, 肖志刚. 利用TCGA数据库构建基于miRNA的结直肠癌列线图预后模型[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 381-388.
[11] 张伟伟, 陈启, 翁和语, 黄亮. 随机森林模型预测T1 期结直肠癌淋巴结转移的初步研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 389-393.
[12] 季鹏程, 鄂一民, 陆晨, 喻春钊. 循环外泌体相关生物标志物在结直肠癌诊断中的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 265-273.
[13] 李佳莹, 王旭丹, 梁雪, 张雷, 李佳英. 1990~2021年中国结直肠癌死亡趋势分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 274-279.
[14] 戈伟, 陈刚. 纳米炭导航行淋巴示踪在结直肠癌TNM分期中淋巴分期价值的临床研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 288-293.
[15] 崔精, 鲍一帆, 沈晓明, 杨增辉, 高森, 鲍传庆. 结直肠癌中circMFSD12对肿瘤细胞功能及5-FU敏感性的调控[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 294-302.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号