-
乳腺癌是女性常见的恶性肿瘤之一,浸润性导管癌是乳腺癌最常见的病理类型,乳腺癌在临床分期、分子生物学分型中的异质性会导致病人预后差异明显。浸润性导管癌的T分期、临床分期与手术切除、新辅助化疗等治疗方式的选择密切相关,雌激素受体(estrogen receptor,ER)、孕激素受体(progestogen receptor,PR)、表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)及增殖细胞相关抗原Ki-67等生物学指标是乳腺癌分子分型的重要依据,不同分型的乳腺癌靶向治疗方式和预后各有不同[1]。因此术前使用影像学对浸润性导管癌肿瘤分期和分子生物学特征的评估十分重要。
随着分子影像学的发展,18F-脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)正电子发射计算机断层扫描(positron emission tomography-computed tomography,PET-CT)在乳腺病变良恶性鉴别、乳腺癌临床分期和分子分型中的应用逐渐广泛。既往研究[2]显示,18F-FDG PET-CT的最大标准摄取值(SUVmax)、肿瘤代谢体积(MTV)及糖酵解总量(TLG)等代谢参数在评估乳腺癌临床分期和分子生物学特征等方面有重要作用,但上述研究未在乳腺癌精准病理学分型的基础上进行研究,且未关注PET-CT代谢参数与Ki-67的关系。本研究回顾性分析了35例共40个乳腺浸润性导管癌原发病灶的PET-CT代谢参数,并与分子生物学指标进行对比研究,进一步分析不同T分期、临床分期和淋巴结转移状态乳腺癌原发病灶的PET-CT代谢参数的差异,探讨PET-CT预测乳腺癌分子生物学特征和临床分期的价值。现作报道。
-
35例共40个乳腺癌病灶均表现为乳腺内软组织结节或肿块,18F-FDG摄取较正常乳腺组织显著增高(见图 1~2)。40个乳腺癌病灶的SUVmax为6.53±2.43,SUVmean为3.96±1.52,MTV为14.50 cm3(5.27 cm3, 31.95 cm3),TLG为33.5 g(16.41 g,83.17 g)。
-
40个乳腺癌原发病灶中,PR(+)27个,PR(-)13个;ER(+)21个,ER(-)19个;HER-2(+)28个,HER-2(-)12个。PR(-)组SUVmax和MTV高于PR(+)组(P < 0.01和P < 0.05);ER(-)组的SUVmax、SUVmean、TLG和MTV均高于ER(+)组(P < 0.05~P < 0.01);HER-2(-)组MTV低于HER-2(+)组,差异有统计学意义(P < 0.05)(见表 1)。40个乳腺癌原发病例中T1~T2期共21例,T3~T4期共19例。T1~T2期肿瘤的SUVmax、SUVmean、TLG和MTV均小于T3~T4期(P < 0.05~P < 0.01);40个乳腺癌病灶中,有腋窝淋巴结转移的病例共26例,无淋巴结转移的病例共14例,有腋窝淋巴结转移组SUVmax,SUVmean和TLG均高于无腋窝淋巴结转移组(P < 0.05~P < 0.01)(见表 1)。40个乳腺癌原发病例临床分期Ⅱ期12例,Ⅲ期11例,Ⅳ期17例,Ⅳ期肿瘤的TLG值高于其他临床分期(P < 0.05),其他指标在不同临床分期病人中差异无统计学意义(P>0.05)(见表 2)。
临床病理指标 n SUVmax SUVmean MTV[M(Q25,Q75)]/cm3 TLG [M(Q25,Q75)]/g PR 阴性 23 8.38±2.19 4.16±1.69 67.8(42.4,243.0) 4.23(3.31,236) 阳性 17 5.45±2.91 3.30±1.49 19.2(14.6,53.2) 5.31(4.81, 16.00) t — 3.64 1.11 2.13* 1.99* P — < 0.01 >0.05 < 0.05 >0.05 ER 阴性 17 7.62±2.12 4.60±1.04 24.2(13.6, 136.6) 67.8(18.9,476.5) 阳性 23 4.83±1.73 2.96±1.08 5.31(4.81,14.9) 18.1(5.74,42.47) t — 4.58 4.82 2.40* 2.22* P — < 0.01 < 0.01 < 0.05 < 0.05 HER-2 阴性 19 5.67±2.56 3.24±1.40 4.98(1.66, 5.31) 9.87(2.51, 42.47) 阳性 21 7.17±2.58 4.14±1.80 16.01(7.71,115) 38.1(16.78,77.42) t — 1.84 0.83 2.04* 3.45* P — >0.05 >0.05 < 0.05 >0.05 T分期 T1~T2 21 5.20±1.90 3.11±1.31 4.97(2.61, 13.4) 17.68(5.20, 21.89) T3~T4 19 9.63±4.16 5.41±2.34 15.10(5.27,192.3) 66.69(25.5,529.5) t — 4.26△ 3.78△ 2.53* 3.60* P — < 0.01 < 0.01 < 0.05 < 0.01 淋巴结转移 有 26 9.91±3.77 7.36±3.75 6.39(3.50,21.69) 20.06(10.08,66.10) 无 14 5.14±2.41 2.96±1.07 9.37(4.43,15.97) 18.06(6.60,37.14) t — 4.27 5.58△ 0.11* 2.34* P — < 0.01 < 0.01 >0.05 < 0.05 *示zc值;△示t′值 表 1 乳腺癌原发灶PET-CT代谢参数与临床病理特征的关系(x±s)
临床分期 n SUVmax SUVmean MTV[M(Q25,Q75)] /cm3 TLG [M(Q25,Q75)]/g Ⅱ期 12 5.87±2.87 3.41±1.21 5.18(4.54,12.1) 18.6(13.8,24.9) Ⅲ期 11 7.93±2.56 4.50±1.25 17.8(6.24,95.3) 17.7(7.46,67.9) Ⅳ期 17 7.08±3.07 4.13±1.44 5.31(2.40,16.2) 32.9(15.6,374) F — 0.38 0.34 3.50* 6.55* P — >0.05 >0.05 >0.05 < 0.05 MS组内 — 28.400 9.080 — — *示Hc值 表 2 不同临床分期乳腺癌原发灶PET-CT代谢参数的比较(x±s)
-
对上述评估乳腺癌生物学特征、临床分期和淋巴结转移中存在统计学差异的代谢参数分别绘制ROC曲线并计算敏感性和特异性。在乳腺癌生物学特征的评估中,PR组SUVmax和MTV的ROC曲线见图 3A,AUC分别为0.792和0.688,SUVmax以6.18为临界值时,敏感性和特异性分别为85.7%和54.5%,MTV以11.7为临界值时,敏感性和特异性分别为71.7%和72.7%。ER组SUVmax、SUVmean、TLG和MTV的ROC曲线见图 3B,AUC分别为0.786、0.766、0.818和0.818,SUVmax以3.06为临界值时敏感性和特异性分别为63.6%和85.7%,SUVmean以6.75为临界值时,敏感性和特异性分别为79.8%和57.1%,TLG以47.5为临界值时,敏感性和特异性分别为63.6%和85.7%,MTV以10.5为临界值时,敏感性和特异性分别为90.0%和71.4%。HER-2组MTV的ROC曲线见图 3C,MTV以6.52为临界值时,敏感性和特异性分别为81.8%和85.7%。在乳腺癌临床分期的评估中、MTV和TLG鉴别乳腺癌临床分期的ROC曲线见图 3D,AUC分别为0.864和0.755,MTV以25.6为临界值时,敏感性和特异性分别为78.0%和89.0%,TLG以12.4为临界值时,敏感性和特异性分别为64.0%和77.0%。在淋巴结转移的评估中,SUVmax、SUVmean和TLG评估乳腺癌淋巴结转移的ROC曲线见图 3E,AUC分别为0.728、0.664和0.700,SUVmax以3.62为临界值时,敏感性和特异性分别为96.0%和60.0%,SUVmean以2.35为临界值时,敏感性和特异性分别为60.0%和70.0%,TLG以31.10为临界值时,敏感性和特异性分别为64.0%和70.0%。
-
40个乳腺癌原发病灶的SUVmax(r=0.783)、MTV(rs=0.868)与肿瘤Ki-67表达呈正相关关系(P < 0.01)。26例有腋窝淋巴结转移的病例中,腋窝淋巴结的SUVmax与相应肿瘤原发灶Ki-67表达呈正相关关系(r=0.857)(P < 0.01)。
18F-FDG PET-CT评估乳腺浸润性导管癌临床及病理特征的研究
Study on the value of 18F-FDG PET-CT in the evaluation of the clinical and pathological features of invasive ductal carcinoma of breast
-
摘要:
目的评估18F-脱氧葡萄糖正电子发射计算机断层扫描(18F-FDG PET-CT)代谢参数与乳腺浸润性导管癌临床病理学特征的关系。 方法回顾性分析术前行18F-FDG PET-CT扫描且经病理学确诊为浸润性导管癌的40个病灶,测量最大标准摄取值(SUVmax)、平均标准摄取值(SUVmean)、肿瘤代谢体积(MTV)并计算糖酵解总量(TLG)。 结果40个浸润性导管癌中,孕激素受体(PR)(-)组SUVmax和MTV高于PR(+)组,雌激素受体(ER)(-)组SUVmax、SUVmean、MTV和TLG均高于ER(+)组,表皮生长因子受体-2(HER-2)(-)组MTV低于HER-2(+)组,T1~T2期肿瘤的SUVmax、SUVmean、TLG和MTV均小于T3~T4期,有腋窝淋巴结转移病例的SUVmax、SUVmean和TLG均高于无腋窝淋巴结转移病例(P < 0.05~P < 0.01)。原发灶的SUVmax、MTV与Ki-67表达呈正相关关系(P < 0.01)。腋窝淋巴结的SUVmax与原发灶Ki-67表达呈正相关关系(P < 0.01)。 结论18F-FDG PET-CT代谢参数能够评估乳腺浸润性导管癌的临床病理特征。 -
关键词:
- 乳腺肿瘤 /
- 体层摄影术 /
- 正电子发射计算机断层扫描 /
- 脱氧葡萄糖
Abstract:ObjectiveTo evaluate the relationship between the metabolic parameters of 18F-deoxyglucose positron emission computed tomography(18F-FDG PET-CT) and clinical and pathological characteristics of invasive ductal carcinoma of breast. MethodsThe clinical data of 40 primary lesions of invasive ductal carcinoma of breast diagnosed by pathology and scanned by 18F-FDG PET-CT before operation were retrospectively analyzed.The max of standardized uptake value(SUVmax), mean of standardized uptake value(SUVmean) and metabolic tumor volume(MTV) of lesions were measured, and the total lesion glycolysis(TLG) of lesions were calculated. ResultsThe SUVmax and MTV of the PR(-) group were higher than those of the PR(+) group.The SUVmax, SUVmean, TLG and MTV of the ER(-) group were higher than those of the ER(+) group.The MTV of the HER-2(-) group was lower than that of HER-2(+) group, the SUVmax, SUVmean, TLG and MTV of the stage T1-T2 tumors were less than those of the stage T1-T2 tumors, and the SUVmax, SUVmean, TLG and MTV in cases with axillary lymph node metastasis were higher than those in cases without axillary lymph node metastasis(P < 0.05 to P < 0.01).The SUVmax and MTV were positively correlated with the expression of Ki-67 in primary lesions(P < 0.01).The SUVmax of axillary lymph nodes was positively correlated with the expression of Ki-67 in the primary lesions(P < 0.01). ConclusionsThe 18F-FDG PET-CT metabolic parameters can evaluate the biological and clinical characterstics of invasive ductal carcinoma of breast. -
表 1 乳腺癌原发灶PET-CT代谢参数与临床病理特征的关系(x±s)
临床病理指标 n SUVmax SUVmean MTV[M(Q25,Q75)]/cm3 TLG [M(Q25,Q75)]/g PR 阴性 23 8.38±2.19 4.16±1.69 67.8(42.4,243.0) 4.23(3.31,236) 阳性 17 5.45±2.91 3.30±1.49 19.2(14.6,53.2) 5.31(4.81, 16.00) t — 3.64 1.11 2.13* 1.99* P — < 0.01 >0.05 < 0.05 >0.05 ER 阴性 17 7.62±2.12 4.60±1.04 24.2(13.6, 136.6) 67.8(18.9,476.5) 阳性 23 4.83±1.73 2.96±1.08 5.31(4.81,14.9) 18.1(5.74,42.47) t — 4.58 4.82 2.40* 2.22* P — < 0.01 < 0.01 < 0.05 < 0.05 HER-2 阴性 19 5.67±2.56 3.24±1.40 4.98(1.66, 5.31) 9.87(2.51, 42.47) 阳性 21 7.17±2.58 4.14±1.80 16.01(7.71,115) 38.1(16.78,77.42) t — 1.84 0.83 2.04* 3.45* P — >0.05 >0.05 < 0.05 >0.05 T分期 T1~T2 21 5.20±1.90 3.11±1.31 4.97(2.61, 13.4) 17.68(5.20, 21.89) T3~T4 19 9.63±4.16 5.41±2.34 15.10(5.27,192.3) 66.69(25.5,529.5) t — 4.26△ 3.78△ 2.53* 3.60* P — < 0.01 < 0.01 < 0.05 < 0.01 淋巴结转移 有 26 9.91±3.77 7.36±3.75 6.39(3.50,21.69) 20.06(10.08,66.10) 无 14 5.14±2.41 2.96±1.07 9.37(4.43,15.97) 18.06(6.60,37.14) t — 4.27 5.58△ 0.11* 2.34* P — < 0.01 < 0.01 >0.05 < 0.05 *示zc值;△示t′值 表 2 不同临床分期乳腺癌原发灶PET-CT代谢参数的比较(x±s)
临床分期 n SUVmax SUVmean MTV[M(Q25,Q75)] /cm3 TLG [M(Q25,Q75)]/g Ⅱ期 12 5.87±2.87 3.41±1.21 5.18(4.54,12.1) 18.6(13.8,24.9) Ⅲ期 11 7.93±2.56 4.50±1.25 17.8(6.24,95.3) 17.7(7.46,67.9) Ⅳ期 17 7.08±3.07 4.13±1.44 5.31(2.40,16.2) 32.9(15.6,374) F — 0.38 0.34 3.50* 6.55* P — >0.05 >0.05 >0.05 < 0.05 MS组内 — 28.400 9.080 — — *示Hc值 -
[1] SINGH S, RAGHAVAN B, GEETHAPRIYA S, et al. PET-CT upstaging of unilateral operable breast cancer and its correlation with molecular subtypes[J]. Indian J Radiol Imaging, 2020, 30(3): 319. doi: 10.4103/ijri.IJRI_59_20 [2] PAYDARY K, SERAJ SM, ZADEH MZ, et al. The evolving role of FDG-PET/CT in the diagnosis, staging, and treatment of breast cancer[J]. Mol Imaging Biol, 2019, 21(1): 1. doi: 10.1007/s11307-018-1181-3 [3] 胡永全, 袁超, 陶新全, 等. 18F-FDG PET/CT检测卵巢癌术后CA125升高病人转移或复发的临床分析[J]. 蚌埠医学院学报, 2020, 45(9): 1163. [4] 母予馨, 张频, 马飞, 等. 乳腺癌原发灶和转移灶受体表达的异质性及其临床意义[J]. 中华肿瘤杂志, 2018, 40(7): 506. doi: 10.3760/cma.j.issn.0253-3766.2018.07.005 [5] 汤泊, 张银, 周锦, 等. 18F-FDG PET-CT代谢参数与乳腺癌临床病理特征的关系[J]. 中华肿瘤杂志, 2017, 39(4): 280. doi: 10.3760/cma.j.issn.0253-3766.2017.04.008 [6] 鲁胜男, 冯彦林, 李雯, 等. 局部晚期乳腺癌18F-FDG PET/CT显像和分子分型与预后相关性研究[J]. 中华肿瘤防治杂志, 2019, 26(5): 324. [7] GARCIA-VICENTE AM, PÉREZ-BETETA J, PÉREZ-GARCÍA VM, et al. Metabolic tumor burden assessed by dual time point 18F-FDG PET/CT in locally advanced breast cancer: relation with tumor biology[J]. Mol Imaging Biol, 2017, 19(4): 636. doi: 10.1007/s11307-016-1034-x [8] QU YH, LONG N, RAN C, et al. The correlation of 18F-FDG PET/CT metabolic parameters, clinicopathological factors, and prognosis in breast cancer[J]. Clin Transl Oncol, 2021, 23(3): 620. doi: 10.1007/s12094-020-02457-w [9] 牛增志. 乳腺癌原发灶18F-FDG PET-CT代谢参数与患者临床病理特征的关系研究[J]. 中国CT与MRI杂志, 2019, 17(4): 79. [10] HIGUCHI T, NISHIMUKAI A, OZAWA H, et al. Prognostic significance of preoperative 18F-FDG PET/CT for breast cancer subtypes[J]. Breast, 2016, 30: 5. doi: 10.1016/j.breast.2016.08.003 [11] 李艳, 代永亮, 张卫善, 等. 18F-FDG PET/CT在乳腺癌诊断和分期中的应用价值[J]. 实用放射学杂志, 2019, 35(9): 1436. doi: 10.3969/j.issn.1002-1671.2019.09.014 [12] EGE AKTAS G, TAŞTEKIN E, SARIKAYA A. Assessment of biological and clinicalaggressiveness of invasive ductal breast cancer using baseline 18F-FDG PET/CT derived volumetric parameters[J]. Nucl Med Commun, 2018, 39(1): 83. doi: 10.1097/MNM.0000000000000779 [13] BORM KJ, VOPPICHLER J, DVSBERG M, et al. FDG/PET-CT-based lymph node atlas in breast cancer patients[J]. Int J Radiat Oncol Biol Phys, 2019, 103(3): 574. doi: 10.1016/j.ijrobp.2018.07.2025 [14] 阳宁静, 任静, 李吉满. 乳腺癌Ⅰ、Ⅱ组淋巴结Ki-67定性、定量表达差异及相关分析[J]. 蚌埠医学院学报, 2018, 43(9): 1125. [15] AN YS, KANG DK, JUNG Y, et al. Volume-based metabolic parameter of breast cancer on preoperative 18F-FDG PET/CT could predict axillary lymph node metastasis[J]. Medicine(Baltimore), 2017, 96(45): e8557. [16] 宋旗, 胡友庭, 杨泳, 等. 乳腺癌组织细胞核增殖抗原的异常表达与病理特征相关性[J]. 中华实验外科杂志, 2020, 37(2): 317. [17] AN YS, KANG DK, JUNG Y, et al. Hormone receptor, human epidermal growth factor receptor-2, and Ki-67 status in primary breast cancer and corresponding recurrences or synchronous axillary lymph node metastases[J]. Surg Today, 2020, 50(7): 657. doi: 10.1007/s00595-019-01831-8 [18] 张倩, 辛军, 李红, 等. 18F-FDG PET/CT显像半定量参数MTV、TLG联合SUV在乳腺癌诊断中的应用价值[J]. 中国临床医学影像杂志, 2016, 27(9): 620. [19] ARSLAN E, CAN TRABULUS D, MERMUT Ö, et al. Alternative volumetric PET parameters for evaluation of breast cancer cases with 18F-FDG PET/CT imaging: Metabolic tumour volume and total lesion glycolysis[J]. J Med Imaging Radiat Oncol, 2021, 65(1): 38. doi: 10.1111/1754-9485.13114 [20] ORSARIA P, CHIARAVALLOTI A, CAREDDA E, et al. Evaluation of the usefulness of FDG-PET/CT for nodal staging of breast cancer[J]. Anticancer Res, 2018, 38(12): 6639. doi: 10.21873/anticanres.13031