Expression of coproporphyrinogen oxidase is associated with detection of upper gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic diagnosis

粪卟啉原氧化酶的表达与 5-氨基乙酰丙酸介导的光动力诊断检测上消化道癌有关

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作者:Kumi Ogihara, Hajime Isomoto, Hiroki Kurumi, Tsutomu Kanda, Mikiko Hashisako, Kazuhiro Tabata, Hiroyuki Ishii, Ken Ohnita, Naoyuki Yamaguchi, Yuko Akazawa, Kayoko Matsushima, Fuminao Takeshima, Masaki Kunizaki, Shigekazu Hidaka, Atsushi Nanashima, Junya Fukuoka, Takeshi Nagayasu, Kazuhiko Nakao

Background

5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer.

Conclusion

Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.

Methods

Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase.

Results

Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors.

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