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Abstract Purpose  In gastric carcinoma, high expression of PRL-3, a protein tyrosine phosphatase, is associated with lymph node metastasis. We studied the relationship between PRL-3 expression and peritoneal metastasis in gastric carcinoma. Methods  Immunohistochemical analysis using the anti-PRL-3 antibody was done in 639 patients with gastric carcinoma including 89 with peritoneal metastases. We then compared the clinicopathologic characteristics of the PRL-3-positive and PRL-3-negative carcinomas. Results   PRL-3 was expressed in 70.4% of the primary gastric carcinomas overall; in 80.9% of the cancers with peritoneal metastasis and in 68.7% of those without peritoneal metastasis (P = 0.020). PRL-3 expression was higher in peritoneal metastasis than in the corresponding primary gastric cancers (P = 0.028). PRL-3 expression was correlated with tumor stage (coefficient = 0.343, P = 0.01) and cancer progression, including lymphatic invasion (coefficient = 0.325, P = 0.02), extent of lymph node metastasis (coefficient = 0.322, P = 0.01), and peritoneal metastasis (coefficient = 0.316, P = 0.03). Patients who were PRL-3-negative had a better survival rate than those who were PRL-3-positive at all stages (stage I: log-rank P = 0.046, Wilcoxon P = 0.048; stage II: log-rank P = 0.035, Wilcoxon P = 0.041; stage III: log-rank P = 0.027, Wilcoxon P = 0.033; stage IV: log-rank P = 0.032, Wilcoxon P = 0.030). Conclusions  Peritoneal metastasis appears to be correlated with PRL-3 expression, tumor stage, lymphatic invasion, and extent of lymph node metastasis. PRL-3 expression was negatively correlated with prognosis in patients with gastric cancer. [ABSTRACT FROM AUTHOR]