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中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (11) : 890 -896. doi: 10.3877/cma.j.issn.1674-0785.2021.11.016

基础研究

基于p53蛋白表达及肿瘤出芽的组织学探讨影响结肠癌预后的独立预测因子
李芳1, 刘月平1, 韩梦雪1, 王贵英2,()   
  1. 1. 050011 石家庄,河北医科大学第四医院病理科
    2. 050011 石家庄,河北医科大学第四医院外二科;050051 石家庄,河北医科大学第三医院胃肠外科
  • 收稿日期:2021-08-05 出版日期:2021-11-15
  • 通信作者: 王贵英

Identification of independent prognostic factors for colon cancer based on p53 protein expression and tumor budding histology

Fang Li1, Yueping Liu1, Mengxue Han1, Guiying Wang2,()   

  1. 1. Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050001, China
    2. Second Department of General Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050001, China; Department of Gastrointestinal Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
  • Received:2021-08-05 Published:2021-11-15
  • Corresponding author: Guiying Wang
引用本文:

李芳, 刘月平, 韩梦雪, 王贵英. 基于p53蛋白表达及肿瘤出芽的组织学探讨影响结肠癌预后的独立预测因子[J/OL]. 中华临床医师杂志(电子版), 2021, 15(11): 890-896.

Fang Li, Yueping Liu, Mengxue Han, Guiying Wang. Identification of independent prognostic factors for colon cancer based on p53 protein expression and tumor budding histology[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(11): 890-896.

目的

探讨p53蛋白表达及肿瘤出芽与结肠癌临床病理特征的关系,确定影响结肠癌预后的独立预测因子。

方法

收集2014年1月至2015年12月于河北医科大学第四医院行根治性手术切除的424例结肠癌患者病历资料。免疫组化Envision法检测p53蛋白表达情况,HE染色评价肿瘤出芽情况。分析p53蛋白表达、肿瘤出芽的影响因素及两者之间的相关性。采用Kaplan-Meier法绘制生存曲线,Cox比例风险模型分析结肠癌患者5年生存率的独立影响因素。

结果

424例结肠癌患者中,野生型220例,突变型204例,突变率为48.11%。单因素分析结果显示,p53突变与肿瘤位置、浸润深度、淋巴结转移、远处转移、血管侵犯、分化程度、临床分期密切相关(P<0.05)。肿瘤出芽分级低度170例(40.09%),中度219例(51.65%),高度35例(8.25%)。单因素分析结果显示,肿瘤出芽与肿瘤大小、浸润深度、淋巴结转移、远处转移、血管侵犯、神经侵犯、分化程度密切相关(P<0.05)。肿瘤出芽级别越高,p53蛋白突变率越高(P<0.05)。多因素Cox回归分析显示,肿瘤浸润深度、远处转移、p53突变状态、肿瘤出芽是结肠癌患者5年生存率的独立影响因素(P<0.05)。

结论

p53突变不仅与结肠癌肿瘤出芽密切相关,而且是影响结肠癌预后的独立预测因素。

Objective

To investigate the relationship between the expression of p53 protein & tumor budding and clinicopathological features of colon cancer, and to determine the independent prognostic factors for colon cancer.

Methods

Data of 424 patients with colon cancer who underwent radical surgical resection at the Fourth Hospital of Hebei Medical University from January 2014 to December 2015 were collected. The protein expression of p53 was detected by immunohistochemistry, and tumor budding was evaluated by hematoxylin and eosin staining. The factors affecting the expression of p53 protein and the budding of tumor and their correlation were analyzed. Kaplan-Meier method was used to draw survivorship curve, and Cox proportional risk model was used to predict independent factors for 5-year survival in colon cancer patients.

Results

Among 424 patients with colon cancer, 220 had wild-type p53 and 204 had mutant p53, with a mutation rate of 48.11%. Univariate analysis showed that p53 mutation was closely related to tumor location, invasion depth, lymph node metastasis, distant metastasis, vascular invasion, differentiation degree, and clinical stage (P<0.05). The grade of tumor budding was low in 170 cases (40.09%), moderate in 219 cases (51.65%), and high in 35 cases (8.25%). Univariate analysis showed that tumor budding was closely related to tumor size, invasion depth, lymph node metastasis, distant metastasis, vascular invasion, nerve invasion, and differentiation degree (P<0.05). The higher the grade of tumor budding, the higher the p53 protein mutation rate (P<0.05). Multivariate Cox regression analysis showed that tumor invasion depth, distant metastasis, p53 mutation status, and tumor budding were independent predictors of 5-year survival (P<0.05).

Conclusion

p53 mutation is not only closely related to the tumor budding in colon cancer, but it is also an independent predictor of the prognosis of colon cancer.

图1 p53蛋白在结肠癌组织中的表达情况(IHC Envision法,×200)。图a为p53突变型;图b为p53野生型
表1 p53蛋白突变及肿瘤出芽情况与结肠癌临床病理特征的关系[例(%)]
项目 例数 p53表达 χ2 P 肿瘤出芽 χ2 P
野生型 突变型 低度 中度 高度
性别 0.000 0.994 1.178 0.555

210 109(51.90) 101(48.10) 80(38.10) 114(54.29) 16(7.60)

214 111(51.87) 103(48.13) 90(42.06) 105(49.07) 19(8.90)
年龄 0.095 0.758 1.345 0.511

<55岁

134 71(53.00) 63(47.01) 51(38.06) 69(51.49) 14(10.45)

≥55岁

290 149(51.38) 141(48.62) 119(41.03) 150(51.72) 21(7.24)
肿瘤位置 10.971 0.001 2.694 0.260

左半结肠

214 94(43.93) 120(56.07) 81(37.85) 111(51.87) 22(10.28)

右半结肠

210 126(60.00) 84(40.00) 89(42.38) 108(51.43) 13(6.19)
肿瘤直径 0.002 0.963 6.178 0.046

<4.13 cm

62 32(51.61) 30(48.39) 17(27.42) 21(33.87) 24(38.71)

≥4.13 cm

362 188(51.93) 174(48.07) 153(42.27) 198(54.70) 11(3.04)
浸润深度 13.901 0.002 17.561 0.004

T1

6 5(83.33) 1(16.67) 2(33.33) 3(50.00) 1(16.67)

T2

30 24(80.00) 6(20.00) 6(20.00) 16(53.33) 8(26.67)

T3

100 53(53.00) 47(47.00) 44(44.00) 46(46.00) 10(10.00)

T4

288 138(47.92) 150(52.08) 118(40.97) 154(53.47) 16(5.56)
淋巴结转移 7.637 0.022 74.505 <0.001

N0

254 137(53.94) 117(46.06) 88(34.65) 158(62.20) 8(3.15)

N1

142 71(50.00) 71(50.00) 78(54.93) 53(37.32) 11(7.75)

N2

28 12(42.86) 16(57.14) 4(14.29) 8(28.57) 16(57.14)
远处转移 10.151 0.001 55.867 <0.001

M0

382 209(54.71) 173(45.29) 165(43.19) 201(52.62) 16(4.19)

M1

42 11(26.19) 31(73.81) 5(11.90) 18(42.86) 19(45.24)
血管侵犯 5.714 0.017 28.853 <0.001

97 40(41.24) 57(58.76) 26(26.80) 51(52.58) 20(20.62)

327 180(55.05) 147(44.95) 144(44.04) 168(51.38) 15(4.59)
神经侵犯 0.068 0.794 21.379 <0.001

83 42(50.60) 41(49.40) 35(42.17) 43(51.81) 19(22.89)

341 178(52.20) 163(47.80) 135(39.59) 176(51.61) 16(4.70)
肿瘤组织分化程度 6.333 0.012 24.650 <0.001

409 217(53.06) 192(46.94) 169(41.32) 213(52.08) 27(6.60)

15 3(20.00) 12(80.00) 1(6.67) 6(40.00) 8(53.33)
临床分期 39.296 <0.001 14.356 0.022

Ⅰ期

33 30(90.91) 3(9.09) 18(54.55) 13(39.39) 2(6.06)

Ⅱ期

215 125(58.14) 90(41.86) 98(45.58) 100(46.51) 17(7.91)

Ⅲ期

134 50(37.31) 84(62.69) 45(33.58) 77(57.46) 12(8.96)

Ⅳ期

42 15(35.71) 27(64.29) 9(21.43) 29(69.05) 4(9.52)
图2 结肠癌组织中肿瘤出芽情况(HE,×200)。图a为低度;图b为中度;图c为高度
表2 结肠癌患者5年生存率与临床病理特征的关系
表3 结肠癌患者5年生存率独立影响因素的多因素Cox回归分析
图3 结肠癌患者5年生存率的Kaplan-Meier生存曲线。图a为浸润深度;图b为远处转移;图c为p53突变情况;图d为肿瘤出芽情况
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