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

Application of rapid immunohistochemistry in the detection of sentinel lymph node low-volume micrometastases after neoadjuvant chemotherapy for breast cancer

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。

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.

关键词

乳腺癌 / 前哨淋巴结 / 新辅助化疗 / 快速免疫组化

Key words

Breast cancer / Sentinel lymph nodes / Neoadjuvant chemotherapy / Rapid immunohistochemistry

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基金资助

无锡市卫健委科技成果与适宜技术推广项目(T202348)