Correlation between ultrasound features and immunohistochemical markers in 710 cases of breast cancer
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摘要:
目的探讨乳腺癌超声特征与免疫组化指标的相关性。 方法回顾性收集710例经病理证实的乳腺癌肿块资料,记录肿块的超声特征:肿块最大径、位置、纵横比、内部回声、后方回声、边界、边缘、形状、钙化、Alder血流分级、淋巴结转移分析免疫组化指标:雌激素受体(ER)、孕激素受体(PR)、增殖细胞核抗原(Ki-67)、人表皮生长因子受体(HER-2),分析超声特征与免疫组化指标之间的相关性。 结果710例乳腺癌肿块中ER、PR、HER-2、Ki-67的阳性率分别为72.5%、64.1%、61.0%、80.3%,且ER与PR表达呈正相关(r=0.697,P < 0.001),ER、PR与Ki-67表达均呈负相关(r=-0.218,P < 0.001;r=-0.216,P < 0.001)。ER、PR在肿块最大径≤2 cm中的阳性率更高,Ki-67在肿块最大径 > 2 cm中的阳性率更高。ER阳性时,肿块纵横比 > 1占比较高,PR阳性时,乳腺癌肿块的超声特征多表现为形状不规则、边界不清晰、后方回声衰减或消失。HER-2、Ki-67阳性时肿块纵横比≤1多见且更容易发生腋窝淋巴结转移。 结论乳腺癌的超声特征与ER、PR、HER-2、Ki-67表达存在相关性,超声表现可以反映肿块的生物学行为,为患者的临床治疗方案选择及术后预后评估提供有力的参考依据。 Abstract:ObjectiveTo investigate the correlation between the ultrasonic features and immunohistochemical parameters in breast cancer. MethodsThe data of 710 cases of breast cancer proved by pathology were collected retrospectively. The sonographic features (the maximum diameter, position, aspect ratio, internal echo, posterior echo, boundary, margin, shape, calcification, Alder blood flow grading, lymph node metastasis) and immunohistochemical parameters (ER, PR, HER-2, Ki-67) were recorded. The correlation between ultrasonic features and immunohistochemical parameters was analyzed. ResultsThe positive rates of ER, PR, HER-2 and Ki-67 were 72.5%, 64.1%, 61.0% and 80.3% in 710 breast cancer masses, respectively. The positive rate of ER and PR was higher in the maximum diameter ≤2 cm, and that of Ki-67 was higher in the maximum diameter > 2 cm. When ER was positive, the ratio of breast cancer was more than 1(P < 0.001). When PR was positive, the ultrasonic features of breast cancer were irregular shape, unclear boundary, attenuation or disappearance of Posterior Echo. When HER-2 and Ki-67 were positive, the ratio of vertical to horizontal was≤1(P < 0.001), and the axillary lymph node metastasis was more likely. ConclusionThe ultrasonic features of breast cancer are correlated with the expressions of ER, PR, HER-2 and Ki-67, which can reflect the biological behavior of the tumor. It provides a powerful reference for the choice of clinical treatment plan and the evaluation of postoperative prognosis. -
Key words:
- breast cancer /
- breast tumor /
- ultrasonography /
- immunohistochemistry /
- diagnosis
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表 1 乳腺癌的病理类型分布情况
Table 1. The distribution of pathological types of breast cancer
病理类型 例数 百分比(%) 浸润性导管癌 565 79.6 导管原位癌 74 10.4 浸润性小叶癌 19 2.7 乳头状癌 20 2.8 粘液癌 19 2.7 乳腺小管癌 3 0.4 髓样癌 9 1.3 乳头Paget’s病 1 0.1 表 2 乳腺癌免疫组化指标表达及相关性
Table 2. Expression and correlation of breast cancer immunohistochemical indicators
分子生物学指标 PR HER-2 - + r/P - + r/P ER 0.697/ < 0.001 -0.104/0.006 - 176 19 60 135 + 79 436 217 298 ER: 雌激素受体; PR: 孕激素受体; HER-2: 人体表皮生长因子受体. 表 3 乳腺癌免疫组化指标表达及相关性
Table 3. Expression and correlation of breast cancer immunohistochemical indexes
分子生物学指标 HER-2 Ki-67 - + r/P - + r/P PR -0.123/0.001 -0.216/ < 0.001 - 79 176 21 234 + 198 257 119 336 Ki-67: 增殖细胞核抗原. 表 4 乳腺癌免疫组化指标表达及相关性
Table 4. Expression and correlation of breast cancer immunohistochemical indexes
分子生物学指标 ER HER-2 - + r/P - + r/P Ki-67 -0.218/ < 0.001 0.097/0.010 - 11 129 68 72 + 184 386 209 361 表 5 乳腺癌超声特征与ER、PR表达的关系
Table 5. Relationship between the ultrasonographic features of breast cancer and the expression of ER and PR
超声特征 n ER χ2 P PR χ2 P - +[n(%)] - +[n(%)] 肿块最大径(cm) 710 6.245 0.012 7.361 0.007 ≤2 396 94 302(76.3) 125 271(68.4) > 2 314 101 213(67.8) 130 184(58.6) 位置 0.45 0.978 1.132 0.889 内上 136 37 99(73.8) 45 91(66.9) 内下 40 11 29(72.5) 12 28(70.0) 外上 346 98 248(71.7) 131 215(62.1) 外下 123 31 92(74.8) 44 79(64.2) 乳晕区 65 18 47(72.3) 23 42(64.6) 肿块纵横比 5.916 0.015 4.38 0.036 > 1 132 25 107(81.1) 37 95(72.0) ≤1 578 170 408(70.6) 218 360(62.3) 内部回声 1.133 0.287 0.823 0.364 均匀 60 20 40(66.7) 20 40(66.7) 不均匀 650 175 475(73.1) 235 415(63.8) 后方回声 2.767 0.096 8.353 0.004 衰减或消失 485 124 361(74.4) 157 328(67.6) 未衰减 225 71 154(68.4) 98 127(56.4) 边界 2.823 0.093 5.636 0.018 清晰 183 59 124(67.8) 79 104(56.8) 不清晰 527 136 391(74.2) 176 351(66.6) 边缘 1.256 0.262 3.595 0.058 光整 24 9 15(62.5) 13 11(45.8) 不光整 686 186 500(72.9) 242 444(64.7) 形状 1.423 0.233 8.28 0.004 规则 36 13 23(63.9) 21 15(41.7) 不规则 674 182 492(73.0) 234 440(65.3) 钙化 0.96 0.327 0.053 0.818 有 305 78 227(74.4) 111 194(63.6) 无 405 117 288(71.1) 144 261(64.4) 血流分级 1.021 0.312 0.138 0.71 0~1级 386 112 274(71.0) 141 245(63.5) 2~3级 324 83 241(74.4) 114 210(64.8) 淋巴结转移情况 3.259 0.071 3.179 0.075 有 256 60 196(76.6) 81 175(68.4) 无 454 135 319(70.3) 174 280(61.7) 表 6 乳腺癌超声特征与HER-2、Ki-67表达的关系
Table 6. Relationship between ultrasonographic features of breast cancer and the expression of HER-2 and Ki-67
超声特征 n HER-2 χ2 P Ki-67 χ2 P - +[n(%)] - +[n(%)] 肿块最大径(cm) 0.006 0.938 4.298 0.038 ≤2 396 155 241(60.9) 89 307(77.5) > 2 314 122 192(61.1) 51 263(83.8) 位置 4.417 0.352 8.813 0.066 内上 136 61 75(55.1) 19 117(86.0) 内下 40 17 23(57.5) 11 29(72.5) 外上 346 136 210(60.7) 73 273(78.9) 外下 123 42 81(65.9) 19 104(84.6) 乳晕区 65 21 44(67.7) 18 47(72.3) 肿块纵横比 11.980 0.001 4.732 0.030 > 1 132 69 63(47.7) 35 97(73.5) ≤1 578 208 370(64.0) 105 473(81.8) 内部回声 0.568 0.451 0.541 0.462 均匀 60 17 43(71.7) 14 46(76.7) 不均匀 650 260 390(60.0) 126 524(80.6) 后方回声 0.087 0.768 3.606 0.058 衰减或消失 485 191 294(60.6) 105 380(78.4) 未衰减 225 86 139(61.8) 35 190(84.4) 边界 0.402 0.526 3.838 0.050 清晰 183 75 108(59.0) 27 156(85.2) 不清晰 527 202 325(61.7) 113 414(78.6) 边缘 0.337 0.562 0.438 0.508 光整 24 8 16(66.7) 6 18(75.0) 不光整 686 269 417(60.8) 134 552(80.5) 形状 0.000 0.987 2.590 0.108 规则 36 14 22(61.1) 5 31(91.2) 不规则 674 263 411(61.0) 135 539(80.0) 钙化 1.954 0.162 1.851 0.174 有 305 110 195(63.9) 53 252(82.6) 无 405 167 238(58.8) 87 318(78.5) 血流分级 0.008 0.927 0.044 0.833 0~1级 386 150 236(61.1) 75 311(80.6) 2~3级 324 127 197(60.8) 65 259(79.9) 淋巴结转移情况 71.784 0.000 4.237 0.040 有 256 47 209(81.6) 40 216(84.4) 无 454 230 224(49.3) 100 354(77.9) -
[1] Rebecca L, Siegel MPH, Kimberly D, et al. Cancer statistics, 2020[J]. CA: Cancer J Clinic, 2020, 70(1): 7-30. doi: 10.3322/caac.21590 [2] Atkins JJ, Appleton CM, Fisher CS, et al. Which imaging modality is superior for prediction of response to neoadjuvant chemotherapy in patients with triple negative breast cancer?[J]. J Oncol, 2013, 2013: 964863. [3] 曹利娟, 包芸, 王文娟, 等. 转移相关蛋白在乳腺癌原发灶与复发/转移灶中的表达及意义[J]. 复旦学报: 医学版, 2020, 47(4): 591-8. doi: 10.3969/j.issn.1672-8467.2020.04.021 [4] Kamranzadeh H, Ardekani RM, Kasaeian A, et al. Association between Ki-67 expression and clinicopathological features in prognosis of breast cancer: a retrospective cohort study[J]. J Res Med Sci, 2019, 24: 30. doi: 10.4103/jrms.JRMS_553_18 [5] Baulies S, Cusidó M, González-Cao M, et al. Hormone receptor and HER2 status: The only predictive factors of response to neoadjuvant chemotherapy in breast cancer[J]. J Obstet Gynaecol, 2015, 35(5): 485-9. doi: 10.3109/01443615.2014.968113 [6] Shokouh TZ, Ezatollah A, Barand P. Interrelationships between Ki67, HER2/neu, p53, ER, and PR status and their associations with tumor grade and lymph node involvement in breast carcinoma subtypes: retrospective-observational analytical study[J]. Medicine: Baltimore, 2015, 94(32): e1359. doi: 10.1097/MD.0000000000001359 [7] 姜文彬, 任甫. 乳腺浸润性导管癌超声征象与生物学指标相关性的研究[J]. 中国临床医学影像杂志, 2017, 28(2): 89-94. doi: 10.3969/j.issn.1008-1062.2017.02.004 [8] 徐乐. 乳腺癌超声图像特征与ER、PR、CerbB-2的相关性研究[D]. 重庆: 重庆医科大学, 2016. [9] 王阿军. 乳腺浸润性导管癌及原位癌超声特征与分子分型的关系分析[D]. 苏州: 苏州大学, 2018. [10] 杨文涛, 步宏. 乳腺癌雌、孕激素受体免疫组织化学检测指南[J]. 中华病理学杂志, 2015, 44(4): 237-9. doi: 10.3760/cma.j.issn.0529-5807.2015.04.005 [11] 步宏, 杨文涛. 乳腺癌HER2检测指南(2009版[)J]. 中华病理学杂志, 2009, 38(12): 836-40. doi: 10.3760/cma.j.issn.0529-5807.2009.12.013 [12] 水若鸿, 杨文涛. 乳腺癌Ki-67阳性指数的检测和评估[J]. 中华病理学杂志, 2013, 42(6): 420-3. doi: 10.3760/cma.j.issn.0529-5807.2013.06.019 [13] 林韵. 乳腺癌超声征象与分子生物学指标相关性的研究进展[J]. 医学综述, 2014, 20(5): 800-3. doi: 10.3969/j.issn.1006-2084.2014.05.011 [14] Sakurai M, Masuda M, Miki Y, et al. Correlation of miRNA expression profiling in surgical pathology materials, with Ki-67, HER2, ER and PR in breast cancer patients[J]. Int J Biol Markers, 2015, 30(2): e190-9. doi: 10.5301/jbm.5000141 [15] 朱磊, 潘颖, 周毅, 等. 乳腺癌原发灶和复发及转移灶中ER、PR、HER-2、Ki67的变化及其临床意义[J]. 中国现代医生, 2018, 56(13): 14-7. https://www.cnki.com.cn/Article/CJFDTOTAL-ZDYS201813005.htm [16] 王雅婷, 姚兰辉. 乳腺癌超声表现与分子免疫组化指标关系研究新进展[J]. 临床超声医学杂志, 2017, 19(9): 623-4. https://www.cnki.com.cn/Article/CJFDTOTAL-LCCY201709020.htm [17] Cha H, Chang YW, Lee EJ, et al. Ultrasonographic features of pure ductal carcinoma in situ of the breast: correlations with pathologic features and biological markers[J]. Ultrason Seoul Korea, 2018, 37 (4): 307-14. http://www.ncbi.nlm.nih.gov/pubmed/29169230 [18] 焦玲玲, 桂琳, 孔祥海. 浸润性乳腺癌患者高频超声声像图特征与免疫组化关系的研究[J]. 皖南医学院学报, 2019, 38(4): 369-72. doi: 10.3969/j.issn.1002-0217.2019.04.020 [19] Kim SH, Seo BK, Lee J, et al. Correlation of ultrasound findings with histology, tumor grade, and biological markers in breast cancer[J]. Acta Oncol, 2008, 47(8): 1531-8. doi: 10.1080/02841860801971413 [20] 刘倩, 丁兀兀, 陈丽, 等. 年轻乳腺癌临床病理特征及其腋窝淋巴结转移的影响因素[J]. 海南医学, 2019, 30(7): 820-3. doi: 10.3969/j.issn.1003-6350.2019.07.002 [21] 邓淼, 刘江波, 张婷, 等. 乳腺癌腋窝淋巴结状态与分子病理特征的关系及临床意义[J]. 实用医学杂志, 2016, 32(12): 1962-5. doi: 10.3969/j.issn.1006-5725.2016.12.020