Protoporphyrinogen oxidase is involved in the fluorescence intensity of 5-aminolevulinic acid-mediated laser-based photodynamic endoscopic diagnosis for early gastric cancer

•We developed laser-based photodynamic endoscopic diagnosis (LPDED) with 5-aminolevulinic acid (ALA) to detect early gastric cancer.•Between the LPDED-positive and negative groups, there was a significant difference in histopathology.•Protoporphyrinogen oxidase (PPOX), involved in the activation of protoporphyrin IX, can affect the fluorescence intensity.•The expression was examined immunohistochemically. PPOX was significantly expressed in tubular adenocarcinoma than in signet-ring cell carcinoma, affecting LPDED fluorescence intensity. Laser-based photodynamic endoscopic diagnosis (LPDED) is a type of endoscopic diagnosis that uses the fluorescence caused by the photochemical reaction that occurs when a fluorescent substance is irradiated by a light of a specific wavelength. Although 5-aminolevulinic acid (5-ALA) can detect early gastric cancer (EGC) during LPDED, there is an unresolved issue of the differences in fluorescence intensity among histopathological types of gastric cancer. Thus, the aim of the present study was to assess whether protoporphyrinogen oxidase (PPOX), involved in the activation of protoporphyrin IX, can affect the fluorescence intensity in EGC. Thirty-three gastric tumor lesions in 30 patients were assessed by LPDED using a prototype endoscope equipped with a blue laser ray to cause excitation following oral 5-ALA administration. The tumors were then resected by endoscopic submucosal dissection or laparoscopic surgery. PPOX expression was examined immunohistochemically in the excised specimens. To explore the mechanisms of histopathological diversity in PPOX and coproporphyrinogen oxidase (CPOX) expression of EGC, immunohistochemical analysis was performed using 75 surgically resected specimens of diverse EGCs. Among the 33 lesions, 26 tumors were detectable by LPDED, whereas seven were undetectable. Between the LPDED-positive and negative groups, there was a significant difference in histopathology. The expression of PPOX was higher in tubular adenocarcinoma (tub) than in signet-ring cell carcinoma (sig). There were significant differences in PPOX and CPOX expression scores of the surgically resected specimens among tub, poorly differentiated adenocarcinoma (por), and sig. PPOX protein expression could be involved in the fluorescence intensity of LPDED in EGC, possibly reflecting histopathological features.