Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV.


Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
28 Jan 2020
Historique:
received: 18 06 2019
accepted: 13 01 2020
entrez: 30 1 2020
pubmed: 30 1 2020
medline: 29 8 2020
Statut: epublish

Résumé

It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

Sections du résumé

BACKGROUND BACKGROUND
It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD).
METHODS METHODS
Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV.
RESULTS RESULTS
Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV.
CONCLUSIONS CONCLUSIONS
Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.

Identifiants

pubmed: 31992267
doi: 10.1186/s12885-020-6537-9
pii: 10.1186/s12885-020-6537-9
pmc: PMC6988364
doi:

Substances chimiques

Fluorescent Dyes 0
Rhodamines 0
DPP4 protein, human EC 3.4.14.5
Dipeptidyl Peptidase 4 EC 3.4.14.5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

64

Subventions

Organisme : Grant-in-Aid(C)
ID : JSPS, 17K09343

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Auteurs

Keiko Yamamoto (K)

Division of Endoscopy, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan.

Shunsuke Ohnishi (S)

Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, 060-8638, Japan. sonishi@pop.med.hokudai.ac.jp.

Takeshi Mizushima (T)

Department of Gastroenterology, Japanese Red Cross Kitami Hospital, N6, E2, Kitami, 090-8666, Japan.

Junichi Kodaira (J)

Department of Gastroenterology, Keiyukai Daini Hospital, N3-7-1, Hondori, Shiroishi-ku, Sapporo, 003-0027, Japan.

Masayoshi Ono (M)

Department of Gastroenterology, Hakodate Municipal Hospital, 10-1, Minato-cho 1, Hakodate, 041-8680, Japan.

Yutaka Hatanaka (Y)

Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan.

Kanako C Hatanaka (KC)

Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan.

Yugo Kuriki (Y)

Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Mako Kamiya (M)

Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Nobuyuki Ehira (N)

Department of Gastroenterology, Japanese Red Cross Kitami Hospital, N6, E2, Kitami, 090-8666, Japan.

Keisuke Shinada (K)

Department of Gastroenterology, Keiwakai Ebetsu Hospital, Ebetsu, 81-81-6, Yoyogi-cho, Ebetsu, 069-0817, Japan.

Hiroaki Takahashi (H)

Department of Gastroenterology, Keiyukai Daini Hospital, N3-7-1, Hondori, Shiroishi-ku, Sapporo, 003-0027, Japan.

Yuichi Shimizu (Y)

Division of Endoscopy, Hokkaido University Hospital, N14, W5, Kita-ku, Sapporo, 060-8648, Japan.

Yasuteru Urano (Y)

Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Japan Agency for Medical Research and Development (AMED)-CREST, 7-1 Ootemachi-1, Chiyoda-ku, Tokyo, 100-0004, Japan.

Naoya Sakamoto (N)

Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, 060-8638, Japan.

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Classifications MeSH