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

doi:10.3969/j.issn.1674-8115.2022.09.016

Abstract

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)

CLC Number:

R445.9

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.

Figures/Tables 5

TrendMD

References 25

1	DU M, NAIR R, JAMIESON L, et al. Incidence trends of lip, oral cavity, and pharyngeal cancers: global burden of disease 1990‒2017[J]. J Dent Res, 2020, 99(2): 143-151.
2	VEGH A, BANYAI D, UJPAL M, et al. Prevalence of diabetes and impaired fasting glycemia in patients with oral cancer: a retrospective study in Hungary[J]. Anticancer Res, 2022, 42(1): 109-113.
3	CHAKRABORTY D, NATARAJAN C, MUKHERJEE A. Advances in oral cancer detection[J]. Adv Clin Chem, 2019, 91: 181-200.
4	ALMANGUSH A, MÄKITIE A A, TRIANTAFYLLOU A, et al. Staging and grading of oral squamous cell carcinoma: an update[J]. Oral Oncol, 2020, 107: 104799.
5	BOSETTI C, CARIOLI G, SANTUCCI C, et al. Global trends in oral and pharyngeal cancer incidence and mortality[J]. Int J Cancer, 2020, 147(4): 1040-1049.
6	TSAI C K, LIN C Y, KANG C J, et al. Nuclear magnetic resonance metabolomics biomarkers for identifying high risk patients with extranodal extension in oral squamous cell carcinoma[J]. J Clin Med, 2020, 9(4): E951.
7	何渝, 金观桥. 影像学对头颈部鳞癌淋巴结转移包膜外侵犯诊断价值的研究进展[J]. 广西医学, 2020, 42(21): 2866-2868, 2875.
	HE Y, JIN G Q. Diagnostic value of imaging for extranodal extension of lymph node metastasis of head and neck squamous cell carcinoma: a literature review[J]. Guangxi Med J, 2020, 42(21): 2866-2868, 2875.
8	BLASCO M A, NOEL C W, TRUONG T, et al. Radiologic-pathologic correlation of major versus minor extranodal extension in oral cavity cancer[J]. Head Neck, 2022, 44(6): 1422-1429.
9	HO T Y, CHAO C H, CHIN S C, et al. Classifying neck lymph nodes of head and neck squamous cell carcinoma in MRI images with radiomic features[J]. J Digit Imaging, 2020, 33(3): 613-618.
10	LEE H R, ROH J, GU G Y, et al. Differential expression of podoplanin in metastatic lymph node is associated with extranodal extension in oropharyngeal cancer[J]. Sci Rep, 2022, 12(1): 3665.
11	LI G P, ZHANG P, WEI T, et al. Prognostic implications of extranodal extension in papillary thyroid carcinomas: a propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging[J]. Surgery, 2022, 171(2): 368-376.
12	EGLOFF-JURAS C, BEZDETNAYA L, DOLIVET G, et al. NIR fluorescence-guided tumor surgery: new strategies for the use of indocyanine green[J]. Int J Nanomedicine, 2019, 14: 7823-7838.
13	季春宜, 尹强, 袁妙贤, 等. 吲哚菁绿荧光成像技术在腹腔镜下肠隔膜手术中的应用研究[J]. 临床小儿外科杂志, 2021, 20(10): 911-915.
	JI C Y, YIN Q, YUAN M X, et al. Application of indocyanine green fluorescent imaging for laparoscopy of intestinal diaphragm [J]. J Clin Pediatr Surg, 2021, 20(10): 911-5.
14	ROTHENBERGER NJ, STABILE LP. Hepatocyte growth factor/c-Met signaling in head and neck cancer and implications for treatment[J]. Cancers, 2017, 9(4): 39.
15	WU J, YUAN Y, TAO X F. Targeted molecular imaging of head and neck squamous cell carcinoma: a window into precision medicine[J]. Chin Med J (Engl), 2020, 133(11): 1325-1336.
16	LIN B, WU J, WANG Y X, et al. Peptide functionalized upconversion/NIR Ⅱ luminescent nanoparticles for targeted imaging and therapy of oral squamous cell carcinoma[J]. Biomater Sci, 2021, 9(3): 1000-1007.
17	WU J, LIU J, LIN B, et al. Met-targeted dual-modal MRI/NIR Ⅱ imaging for specific recognition of head and neck squamous cell carcinoma[J]. ACS Biomater Sci Eng, 2021, 7(4): 1640-1650.
18	SCHOUW H M, HUISMAN L A, JANSSEN Y F, et al. Targeted optical fluorescence imaging: a meta-narrative review and future perspectives[J]. Eur J Nucl Med Mol Imaging, 2021, 48(13): 4272-4292.
19	COLEVAS A D, YOM S S, PFISTER D G, et al. NCCN guidelines insights: head and neck cancers, version 1.2018[J]. J Natl Compr Canc Netw, 2018, 16(5): 479-490.
20	BHALLI H, CHEN S Q, DAY A, et al. Factors associated with lymph node count in mucosal squamous cell carcinoma neck dissection[J]. Laryngoscope, 2021, 131(7): 1516-1521.
21	ABDEL-HALIM C N, ROSENBERG T, DYRVIG A K, et al. Diagnostic accuracy of imaging modalities in detection of histopathological extranodal extension: a systematic review and meta-analysis[J]. Oral Oncol, 2021, 114: 105169.
22	TIRELLI G, DE GROODT J, SIA E, et al. Accuracy of the Anatomage Table in detecting extranodal extension in head and neck cancer: a pilot study[J]. J Med Imaging (Bellingham), 2021, 8(1): 014502.
23	AIKEN A H, POLIASHENKO S, BEITLER J J, et al. Accuracy of preoperative imaging in detecting nodal extracapsular spread in oral cavity squamous cell carcinoma[J]. AJNR Am J Neuroradiol, 2015, 36(9): 1776-1781.
24	PHAM T D, WATANABE Y, HIGUCHI M, et al. Texture analysis and synthesis of malignant and benign mediastinal lymph nodes in patients with lung cancer on computed tomography[J]. Sci Rep, 2017, 7: 43209.
25	ZOUMALAN R A, KLEINBERGER A J, MORRIS L G, et al. Lymph node central necrosis on computed tomography as predictor of extracapsular spread in metastatic head and neck squamous cell carcinoma: pilot study[J]. J Laryngol Otol, 2010, 124(12): 1284-1288.

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）

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）

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

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

[1]	JIANG Ying-ying1, 2, QIN Xing1, ZHANG Jian-jun1, CHEN Wan-tao1. Expression of long noncoding RNA COL11A1-208 in oral squamous cell carcinoma and its clinical significance [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2020, 40(10): 1334-1339.
[2]	JU Hui-jun, PAN Yu, ZHANG Yi-fan. Advances of quantitative detection of islet β-cells by molecular imaging [J]. , 2016, 36(1): 119-.
[3]	CHEN Ying, XU Li-jun, GONG Zhu-lin, et al. Application of image processing and analysis techniques in molecular imaging [J]. , 2015, 35(4): 605-.
[4]	LIU Shuai, ZHANG Yi-fan. Research progress of radionuclide molecular imaging in pancreatic beta cells [J]. , 2013, 33(2): 245-.
[5]	PAN Yu, ZHANG Yi-fan. Application of radionuclide reporter gene imaging in therapeutic gene monitoring [J]. , 2012, 32(11): 1512-.
[6]	HUANG Gang, LIU Jian-jun. Molecular imaging: key carrier of translational medicine [J]. , 2010, 30(9): 1021-.