Down-regulation of GRIM-19 is associated with STAT3 overexpression in breast carcinomas.

To evaluate the association of gene associated with retinoic-interferon-induced mortality 19 (GRIM-19) with clinicopathologic features as well as its target gene signal transducer and activator of transcription 3 (STAT3) in patients with breast cancer, GRIM-19 and STAT3 expression was measured immunohistochemically in 108 breast samples and by Western blotting in 20 breast cancer tissues and corresponding nontumorous tissues. Expression of GRIM-19 was severely depressed in the carcinomas relative to matched nontumorous tissues (P < .001), and STAT3 was overexpressed in breast cancer tissues (P < .001), conclusions supported by Western blot analysis. Nonexpression of GRIM-19 was significantly associated with lymph node metastasis (P < .001), advanced tumor-node-metastasis stage (P = .02), and triple-negative phenotype (P = .03). Furthermore, down-regulation of GRIM-19 correlated with STAT3 overexpression (r = 0.56; P < .001). Thus, GRIM-19 is suppressed in primary breast carcinomas, with a corresponding increase in STAT3 activity.