Abstract
Background. Photodynamic diagnosis (PDD) with 5-aminolevulinic acid (ALA) was used to detect peritoneal metastasis (PM). This study was done to verify the roles of the expressions of the peptide transporter PEPT1 and ATP-binding cassette transporter ABCG2 genes on the selection of patients in ALA PDD. Methods. The study group comprised 138 patients with PM. After oral administration of 5-ALA, PM was evaluated by PDD. Tissue protoporphyrin IX (PpIX) levels, and PEPT1/ABCG2 mRNA expressions were determined. Results. The tumor detection rate on PDD was 45.6% (63/138). PDD is a safe technique for the detection of PM from ovarian cancer, mesothelioma, and colorectal cancer. PpIX levels of ALA-PDD-positive PM were significantly higher than those of ALA-PDD-negative PM. The PpIX levels in PM that simultaneously expressed PEPT1 and ABCG2 mRNA were significantly higher than those in PM that expressed either PEPT1 or ABCG2 mRNA, as well as PM that expressed neither PEPT1 nor ABCG2 mRNA. PM with PEPT1 mRNA up-regulation showed simultaneous up-regulation of ABCG2 mRNA. PpIX accumulates in PM with PEPT1 up-regulation. At the same time, PpIX may be excreted into stromal tissue through ABCG2 transporter, resulting in the accumulation of excess PpIX in the stromal tissue near cancer cells. Conclusions. Preoperative evaluations of the expressions of the PEPT1 and ABCG2 genes by RT-PCR methods might facilitate the selection of patients most likely to benefit from ALA-PDD.
Highlights
Peritoneal metastasis (PM) has been considered a terminal disease, and palliative chemotherapy and/or best supportive care wass widely used for treatment
We previously reported that the peptide transporter PEPT1 (SLC15A1, aminolevulinic acid (ALA) influx transporter) and ATPbinding cassette (ABC) transporter ABCG2 genes play pivotal roles in the accumulation of protoporphyrin IX (PpIX) in gastric cancer cell lines[9]
Experimental and clinical studies have demonstrated that ALA Photodynamic diagnosis (PDD) can detect peritoneal metastasis (PM) from different cancers[5, 6, 8]
Summary
Peritoneal metastasis (PM) has been considered a terminal disease, and palliative chemotherapy and/or best supportive care wass widely used for treatment. The detection of small PM invisible on white light inspection before CRS is mandatory to perform complete cytoreduction. The detection of small PM was significantly enhanced by administration of 5aminolevulinic acid (ALA) followed by fluorescence assessment in these studies[5]. After high-dose administration of ALA, PpIX accumulates in cancer cells and emits red fluorescence under violet light excitation at 405 nm[6]. PDD is used to detect PM from gastric cancer and serous carcinoma[7,8]. We previously reported that the peptide transporter PEPT1 (SLC15A1, ALA influx transporter) and ATPbinding cassette (ABC) transporter ABCG2 (porphyrin efflux transporter) genes play pivotal roles in the accumulation of PpIX in gastric cancer cell lines[9]. A major aim was to clarify the key molecules in PpIX accumulation after oral administration of ALA
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