Loss of promyelocytic leukemia protein in human gastric cancers.

To clarify the clinical implications of promyelocytic leukemia (PML) expression in gastric carcinomas, the expression of PML was analyzed in large series of gastric carcinoma by immunohistochemistry, western blotting and reverse transcription-PCR. PML protein expression was reduced or abolished in gastric carcinomas (31.7 and 10.6%, respectively) by immunohistochemistry. PML protein loss was associated with more lymphatic invasion, higher pTNM stage, and worse patient survival. Only one gastric carcinoma cell line showed loss of PML, and the PML protein re-appeared after the treatment of proteasome inhibitor in this cell line. We conclude that PML protein loss occurs in a minority of gastric carcinomas during carcinogenesis and progression, and suggest the proteasome-dependent pathway as a mechanism of PML protein loss.