快速免疫组化在乳腺癌新辅助化疗后前哨淋巴结低容积微转移灶检测中的应用

doi:10.6040/j.issn.1671-7554.0.2025.0136

摘要/Abstract

摘要： 目的通过快速免疫组化(rapid immunohistochemistry, RD-IHC)技术检测乳腺癌新辅助化疗(neoadjuvant chemotherapy, NAC)后前哨淋巴结(sentinel lymph nodes, SLN)转移灶的大小和类型,分析RD-IHC检测的准确率和假阴性率以及与临床病理特征的关系。方法采用RD-IHC一步法检测乳腺癌NAC后SLN术中冰冻切片CK(pan)的表达,分析比较术中苏木精-伊红(intraoperative hematoxylin and eosin, IH)、RD-IHC、常规苏木精-伊红(hematoxylin and eosin, HE)加免疫组化(routine HE plus IHC,RHPI)三种方法对于SLN宏转移、微转移和孤立肿瘤细胞(isolatedtumor cells, ITCs)的检出率(detection rate, DR),并进一步分析与假阴性率(false negative rate, FNR)相关的临床病理特征。结果共收集393 例接受 NAC 的SLN活检标本,检测出1 106个淋巴结,平均每例 SLN 活检数量 1~5 个。IH 检出SLN转移98 例,RD-IHC 检出123 例,RHPI检出133 例。其中,IH 对于SLN微转移和ITCs的DR分别为4.6%和3.1%,FNR为26.3%(35/133),22 例诊断延迟;RD-IHC对于SLN微转移和ITCs的DR为8.8%和6.2%,FNR为7.5%(10/133),无延迟诊断病例;RHPI对于SLN微转移和ITCs的 DR为8.9%和7.6%。与IH相比,RD-IHC能提高低容积微转移灶的DR,降低FNR。在亚组分析中,RD-IHC假阴性主要常见于ER+、PR+、HER2-、P53野生型和低Ki67表达的病例,含有微转移灶的SLN活检标本的FNR明显高于宏转移组。每例SLN 活检数量达到 3枚以上时,SLN 活检的DR明显提高,FNR下降。结论 RD-IHC能在短时间内明显提高乳腺癌NAC后SLN转移的术中诊断准确率,尤其是对于低容积微转移病例;RD-IHC能有效降低延迟诊断率,并将FNR维持在可控范围内,从而避免不必要的二次手术,有效指导临床手术方式的选择。

关键词: 乳腺癌, 前哨淋巴结, 新辅助化疗, 快速免疫组化

Abstract: Objective To assess the size and type of sentinel lymph node(SLN)metastases after neoadjuvant chemotherapy(NAC)for breast cancer using rapid immunohistochemistry(RD-IHC)technology, and to analyze the accuracy and false negative rate(FNR)of RD-IHC detection, as well as its correlation with clinical pathological characteristics. Methods The one-step RD-IHC method was used to detect the expression of CK(pan)in intraoperative frozen sections of SLNs after NAC for breast cancer. The detection rates(DR)of three methods-intraoperative hematoxylin and eosin(IH), RD-IHC, and routine hematoxylin and eosin(HE)plus immunohistochemistry(RHPI)-for SLN macro-metastases, micro-metastases, and isolated tumor cells(ITCs)were compared and analyzed, and the clinical pathological characteristics associated with FNR were further investigated. Results A total of 393 SLN biopsy specimens from patients undergoing NAC were collected, and 1,106 lymph nodes were detected, with an average of 1 to 5 SLN biopsies per case. IH detected 98 cases of SLN metastases, RD-IHC detected 123 cases, and RHPI detected 133 cases. Among them, the DR of IH for SLN micro-metastases and ITCs was 4.6% and 3.1%, respectively, with an FNR of 26.3%(35/133)and 22 delayed diagnoses, the DR of RD-IHC for SLN micro-metastases and ITCs was 8.8% and 6.2%, respectively, with an FNR of 7.5%(10/133)and no delayed diagnosis cases, the DR of RHPI for SLN micro-metastases and ITCs was 8.9% and 7.6%, respectively. Compared with IH, RD-IHC improved the DR of low-volume micro-metastases and reduced the FNR. In subgroup analysis, RD-IHC false negatives were mainly observed in cases with estrogen receptor(ER)-positive, progesterone receptor(PR)-positive, HER2-negative, P53 wild-type, and low Ki67 expression, and the FNR of SLN biopsy specimens containing micro-metastases was significantly higher than that of the macro-metastasis group. When the number of SLN biopsies per case reached more than 3, the DR of SLN biopsy significantly increased and the FNR decreased. Conclusion RD-IHC can significantly improve the intraoperative diagnostic accuracy of SLN metastasis after NAC in breast cancer within a short period of time, especially for cases with low-volume micro-metastasis. RD-IHC can effectively reduce the rate of delayed diagnosis and maintain the FNR within a controllable range, thereby avoiding unnecessary secondary surgery and effectively guiding the selection of clinical surgical methods.

Key words: Breast cancer, Sentinel lymph nodes, Neoadjuvant chemotherapy, Rapid immunohistochemistry

中图分类号:

祁秀敏,肖燕,孙屏. 快速免疫组化在乳腺癌新辅助化疗后前哨淋巴结低容积微转移灶检测中的应用[J]. 山东大学学报 (医学版), 2026, 64(6): 50-59.

QI Xiumin, XIAO Yan, SUN Ping. Application of rapid immunohistochemistry in the detection of sentinel lymph node low-volume micrometastases after neoadjuvant chemotherapy for breast cancer[J]. Journal of Shandong University (Health Sciences), 2026, 64(6): 50-59.

参考文献

[1] 杨丽萍, 龚镱, 朱进. 乳腺癌患者新辅助化疗后行靶向腋窝切检术的研究进展[J]. 实用癌症杂志, 2022, 37(12): 2081-2085. YANG Liping, GONG Yi, ZHU Jin. Research progress on targeted axillary resection after neoadjuvant chemothe-rapy in breast cancer patients[J]. The Practical Journal of Cancer, 2022, 37(12): 2081-2085.
[2] 金成龙, 张建国. 乳腺癌新辅助化疗后前哨淋巴结活检的研究进展[J]. 临床外科杂志, 2022, 30(4): 386-389. JIN Chenglong, ZHANG Jianguo. Research progress on sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer[J]. Journal of Clinical Surgery, 2022, 30(4): 386-389.
[3] 刘雅倩, 冯丽, 郭飞跃, 等. 新辅助化疗后腋窝淋巴结转阴的乳腺癌患者进行前哨淋巴结活检可行性[J]. 国际外科学杂志, 2023, 50(2): 86-93. LIU Yaqian, FENG Li, GUO Feiyue, et al. Feasibility of sentinel lymph node biopsy in breast cancer patients with negative axillary lymph nodes after neoadjuvantchemotherapy[J]. International Journal of Surgery, 2023, 50(2): 86-93.
[4] Alors RJ, Sanz VS, Fernández GFJ, et al. Sentinel lymph node biopsy after neoadjuvantchemotherapy in cN0 breast cancer: impact of HER2-positive status on survival[J].Eur J Breast Health, 2024, 20(2): 94-101.
[5] Daniel BL, Claire T, Antoine BF, et al. Incorporating lymphovenous anastomosis in clinically node-positive women receiving neoadjuvant chemotherapy: a shared decision-making model and nuanced approached to the axilla[J]. Curr Oncol, 2023, 30(4): 4041-4051.
[6] Barkur S, Notingher I, Rakha E. Intra-operative assessment of sentinel lymph nodes for breast cancer surgery: an update[J]. Surg Oncol, 2022, 40: 101678. doi: 10.1016/j.suronc.2021.101678
[7] Lee J, Park S, Bae SJ, et al. Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy[J]. Breast Cancer Res, 2024, 26(1): 120-130.
[8] Segnan N, Minozzi S, Ponti A, et al. Estimate of false-positive breast cancer diagnoses from accuracy studies: a systematic review[J]. J ClinPathol, 2017, 70(4): 282-294.
[9] Wang K, Ren Y, Huang R, et al. Application of intra-operative frozen section examination in the management of female breast cancer in China: a nationwide, multicenter 10-year epidemiological study[J]. World J Surg Oncol, 2014, 12: 225-233. doi: 10.1186/1477-7819-12-225
[10] Wong W, Rubenchik I, Nofech-Mozes S, et al. Intra-operative assessment of sentinel lymph nodes in breast cancer patients post-neoadjuvanttherapy[J]. Technol Cancer Res Treat, 2019, 18: 1533033818821104. doi: 10.1177/1533033818821104
[11] Lyman G, Giuliano AE, Somerfield MR, et a1. American Society of Clinical Oncology guiedeline recommendations for sentinel lymph node biopsy in early-stage breast cancer[J]. J Clin Oncol, 2005, 23(30): 7703-7720.
[12] Akay CL, Albarracin C, Torstenson T, et al. Factors Impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer[J]. Breast J, 2018, 24(1): 28-34.
[13] Hennessy BT, Hortobagyi GN, Rouzier R, et al. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy[J]. J Clin Oncol, 2005, 23(36): 9304-9311.
[14] Moo TA, Edelweiss M, Hajiyeva S, et al. Is low-volume disease in the sentinel node after neoadjuvantchemotherapy an indication for axillary dissection?[J]. Ann Surg Oncol, 2018, 25(6): 1488-1494.
[15] Grabenstetter A, Moo TA, Hajiyeva S, et al. Accuracy of intraoperative frozen section of sentinel lymph nodes after neoadjuvant chemotherapy for breast carcinoma[J]. Am J SurgPathol, 2019, 43(10): 1377-1383.
[16] Dingemans SA, de Rooij PD, van der Vuurst de Vries RM, et al. Validation of six nomograms for predicting non-sentinel lymph node metastases in a Dutch breast cancer population[J]. Ann Surg Oncol, 2016, 23(2): 477-481
[17] Jeruss JS, Newman LA, Ayers GD, et al. Factors predicting additional disease in the axilla in patients with positive sentinel lymph nodes after neoadjuvantchemotherapy[J]. Cancer, 2008, 112(12): 2646-2654
[18] Gimbergues P, Abrial C, Durando X, et al. Clinicopa-thological factors and nomograms predicting nonsentinel lymph node metastases after neoadjuvant chemotherapy in breast cancer patients[J]. Ann Surg Oncol, 2009, 16(7): 1946-1951.
[19] Chun JW, Kim J, Chung I, et al. Nonsentinel node metastasis prediction during surgery in breast cancer patients with one to three positive sentinel node(s)following neoadjuvant chemotherapy[J]. Sci Rep, 2023, 13(1): 4480. doi: 10.1038/s41598-023-31628-2
[20] Kang YJ, Park JH, Ju YW, et al. A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery[J]. Sci Rep, 2022, 12(1): 12141. doi: 10.1038/s41598-022-16538-z
[21] Aragon-Sanchez S, Oliver-Perez MR, Madariaga A, et al. Accuracy and limitations of sentinel lymph node biopsy after neoadjuvant chemotherapyin breast cancer patients with positive nodes[J]. Breast J, 2022: 1507881. doi: 10.1155/2022/1507881
[22] Ma L, Chen HY, He JJ, et al. The nodal positivity rate in breast pCR patients with initially, clinically node-negative breast cancer after neoadjuvant systemic therapy: a systematic review and meta-analysis[J]. Front Oncol, 2023, 13: 1167912. doi: 10.3389/fonc.2023.1167912
[23] Ahram H, Hyeong GM, Jisun K, et al. Reliability of sentinel lymph node biopsy after neoadjuvant chemothe-rapy in breast cancer patients[J]. J Breast Cancer, 2013, 16(4): 378-385.
[24] Elshanbary AA, Awad AA, Abdelsalam A, et al. The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis[J]. Environ Sci Pollut Res Int, 2022, 29(32): 47931-47941.
[25] 刘梅, 李席如, 宋欣, 等. 术中快速直接免疫组化在乳腺病变和前哨淋巴结诊断中的应用[J]. 诊断病理学杂志, 2018, 25(3): 170-176. LIU Mei, LI Xiru, SONG Xin, et al. Application of intraoperative rapid direct immunohistochemistry in the diagnosis of breast lesions and sentinel lymph nodes[J]. Chinese Journal of Diagnostic Pathology, 2018, 25(3): 170-176.
[26] 尹明英, 李珀, 胡鹏然, 等. 一步核酸扩增和快速直接免疫组化在乳腺癌前哨淋巴结术中的诊断价值[J]. 现代肿瘤医学, 2024, 32(12): 2218-2223. YIN Mingying, LI Po, HU Pengran, et al. Diagnostic value of one-step nucleic acid amplification and rapid direct immunohistochemistry in breast cancer sentinel lymph node surgery[J]. Journal of Modern Oncology, 2024, 32(12): 2218-2223.
[27] 任翡, 平波, 陈颖, 等. 乳腺癌术中腋窝前哨淋巴结细胞学印片快速免疫细胞化学检查的应用价值[J]. 中华病理学杂志, 2022, 51(5): 444-446. REN Fei, PING Bo, CHEN Ying, et al.Application value of rapid immunocytochemical examination of axillary sentinel lymph node cytology prints during breast cancer surgery[J]. Chinese Journal of Pathology, 2022, 51(5): 444-446.
[28] Terata K, Saito H, Nanjo H, et al. Novel rapid-immunohistoehemistry using an alternating current electric field for intraoperative diagnosis of sentinel lymph nodes in breast cancer[J]. Sci Rep, 2017, 7(1): 2810-2819.

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