荧光探针cMBP⁃ICG检测口腔鳞状细胞癌颈部淋巴结转移及包膜外侵犯的探索性研究

doi:10.3969/j.issn.1674-8115.2022.09.016

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (9): 1296-1302.doi: 10.3969/j.issn.1674-8115.2022.09.016

• 论著 · 临床研究 • 上一篇

荧光探针cMBP⁃ICG检测口腔鳞状细胞癌颈部淋巴结转移及包膜外侵犯的探索性研究

杨琳¹(), 王晶波¹, 黄小娟², 任继亮¹, 袁瑛¹, 陶晓峰¹()

^1.上海交通大学医学院附属第九人民医院放射科，上海 200011
^2.上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科，上海 200011

收稿日期:2022-05-24 接受日期:2022-08-28 出版日期:2022-09-28 发布日期:2022-09-28
通讯作者: 陶晓峰 E-mail:541589194@qq.com;cjr.taoxiaofeng@vip.163.com
作者简介:杨　琳（1998—），女，硕士生；电子信箱：541589194@qq.com。
基金资助:
国家自然科学基金(91859202);上海市高水平地方高校创新团队(SHSMU-ZDCX20210402)

Exploratory study on detection of cervical lymph node metastasis and extra-nodal extension of oral squamous cell carcinoma using fluorescent probe cMBP-ICG

YANG lin¹(), WANG Jingbo¹, HUANG Xiaojuan², REN Jiliang¹, YUAN ying¹, TAO Xiaofeng¹()

^1.Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
^2.Department of Oral Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

Received:2022-05-24 Accepted:2022-08-28 Online:2022-09-28 Published:2022-09-28
Contact: TAO Xiaofeng E-mail:541589194@qq.com;cjr.taoxiaofeng@vip.163.com
Supported by:
National Natural Science Foundation of China(91859202);Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20210402)

摘要/Abstract

摘要：

目的·探索利用表面涂抹式荧光探针细胞间充质-上皮转化因子（cellular-mesenchymal epithelial transition factor，c-Met）结合肽（c-Met-binding peptide，cMBP）-吲哚菁绿（indocyanine green，ICG）实现术中实时荧光成像诊断口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）颈部淋巴结转移及淋巴结包膜外侵犯（extra-nodal extension，ENE）的可行性。方法·选取5名上海交通大学医学院附属第九人民医院原发性OSCC患者作为研究对象，通过制备、配制荧光探针cMBP-ICG，采用表面涂抹法对入组的患者颈部淋巴结清扫切除的可疑淋巴结进行实时荧光成像。收集并整理患者临床资料、病理结果及淋巴结实时荧光成像的荧光强度（fluorescence intensity，FI）数据，并根据cMBP-ICG实时荧光成像的FI对淋巴结转移与ENE进行预测。结果·术中对可疑淋巴结进行cMBP-ICG实时荧光成像，获得不同FI的实时成像结果。对5例患者的49个可疑淋巴结的分析结果显示，cMBP-ICG预测淋巴结转移的敏感度为100%，特异度为84%，阳性预测值（positive predictive value，PPV）为67%，阴性预测值（negative predictive value，NPV）为100%。cMBP-ICG预测淋巴结ENE的敏感度为100%，特异度为93%，PPV为63%，NPV为100%。结论·表面涂抹式荧光探针cMBP-ICG术中实时荧光成像能较为有效地识别OSCC转移淋巴结及ENE，可作为术中诊断淋巴结转移及ENE的辅助方法。

关键词: 口腔鳞状细胞癌, 淋巴结包膜外侵犯, 实时荧光成像, 分子影像, 细胞间充质-上皮转化因子

Abstract:

Objective ·To explore the feasibility of intraoperative real-time fluorescence imaging in the diagnosis of oral cancer cervical lymph node metastasis and extra-nodal extension (ENE) in the patients with oral squamous cell carcinoma (OSCC) by using the surface-smeared fluorescent probe cellular-mesenchymal epithelial transition factor (c-Met)?binding peptide (cMBP)? indocyanine green (ICG). Methods ·The five patients with primary OSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were selected as the research subjects. The fluorescent probe cMBP-ICG was prepared, and real-time fluorescence imaging was performed by surface smear method on the suspicious lymph nodes of the enrolled patients who underwent neck lymph node dissection. The clinical information, the pathological results and the fluorescence intensity (FI) values of lymph node real-time fluorescence imaging were collected and sorted, and lymph node metastasis and ENE were predicted according to the FIs of cMBP-ICG real-time fluorescence imaging. Results ·Intraoperative cMBP-ICG real-time fluorescence imaging of suspicious lymph nodes were performed, and imaging results of different FIs were obtained in real time. The results of 49 suspicious lymph nodes in the 5 patients showed that the sensitivity of cMBP-ICG in predicting lymph node metastasis was 100%, the specificity was 84%, the positive predictive value was 67%, and the negative predictive value was 100%. The sensitivity of cMBP-ICG in predicting lymph node ENE was 100%, the specificity was 93%, the positive predictive value was 63%, and the negative predictive value was 100%. Conclusion ·Intraoperative cMBP-ICG real-time fluorescence imaging can effectively identify lymph node metastatic and ENE in OSCC, which can provide an auxiliary method for intraoperative diagnosis of lymph node metastasis and ENE.

Key words: oral squamous cell carcinoma (OSCC), extra-nodal extension (ENE), real-time fluorescence imaging, molecular imaging, cellular-mesenchymal epithelial transition factor (c-Met)

中图分类号:

R445.9

杨琳, 王晶波, 黄小娟, 任继亮, 袁瑛, 陶晓峰. 荧光探针cMBP⁃ICG检测口腔鳞状细胞癌颈部淋巴结转移及包膜外侵犯的探索性研究[J]. 上海交通大学学报（医学版）, 2022, 42(9): 1296-1302.

YANG lin, WANG Jingbo, HUANG Xiaojuan, REN Jiliang, YUAN ying, TAO Xiaofeng. Exploratory study on detection of cervical lymph node metastasis and extra-nodal extension of oral squamous cell carcinoma using fluorescent probe cMBP-ICG[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(9): 1296-1302.

图/表 5

图1 患者入组流程Note： ECOG—Eastern Cooperative Oncology Group.

Fig 1 Patient enrollment process

表1 患者基本资料

Tab 1 Basic data of the patients

ID	Gender	Age/year	Tumour site	Pathology stage	Smoking status	Alcohol consumption	Lymphatic metastasis/ n （%）	ENE/ n （%）
1	Female	48	Left lingual margin	T3N1M0	Never smoking	Never regular	1 （2.3）	0 （0）
2	Male	57	Right lingual margin	T3N1M0	Never smoking	Never regular	1 （10.0）	1 （10.0）
3	Male	58	Right buccal mucosa	T3N1M0	Never smoking	Never regular	2 （5.3）	1 （2.6）
4	Female	67	Right lingual margin	T2N0M0	Never smoking	Never regular	0 （0）	0 （0）
5	Male	72	Mouth floor mucosa	T1N2M0	Never smoking	Never regular	8 （16.3）	3 （6.1）

图2 可疑淋巴结术中实时荧光成像及H-E染色Note： A. White light images of a lymph node containing metastasis with ENE and a non-metastatic lymph node. B. Real-time fluorescence imaging of a lymph node containing metastasis with ENE and a non-metastatic lymph node. C. Pseudo color real-time fluorescence imaging of a lymph node containing metastasis with ENE and a non-metastatic lymph node. D. Signal-to-noise ratio map of real-time fluorescence imaging of a lymph node containing metastasis with ENE and a non-metastatic lymph node. E. H-E staining of a lymph node containing metastasis with ENE and a non-metastatic lymph node. The red dotted lines indicate the direction of pathological section. The white arrows point to the area indicated by fluorescence imaging as positive, and the black arrows point to the area confirmed by pathology as positive.

Fig 2 Intraoperative real-time fluorescence imaging and H-E staining of suspicious lymph nodes

图3 荧光探针诊断效能的ROC曲线Note： A/B. ROC curves of diagnosis efficacy of lymph node metastasis (A) and ENE (B) by using fluorescent probes.

Fig 3 ROC curves of diagnostic efficacy of fluorescent probes

表2 cMBP-ICG实时荧光成像与临床医师经验判断对淋巴结转移与ENE的诊断效能

Tab 2 Diagnostic efficacies of cMBP-ICG real-time fluorescence imaging and clinicians' experiences in lymph node metastasis and ENE

Item	cMBP-ICG diagnostic efficacy		Clinician's empirical diagnostic efficacy
Item	Lymphatic metastasis	ENE	Lymphatic metastasis	ENE
Sensitivity/%	100	100	75	80
Specificity/%	84	93	100	93
PPV/%	67	63	100	57
NPV/%	100	100	93	98
AUC （95%CI）	0.96 （0.91‒1.00）	0.97 （0.92‒1.00）	N/A	N/A

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荧光探针cMBP⁃ICG检测口腔鳞状细胞癌颈部淋巴结转移及包膜外侵犯的探索性研究

Exploratory study on detection of cervical lymph node metastasis and extra-nodal extension of oral squamous cell carcinoma using fluorescent probe cMBP-ICG

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