Coordinated expression of activated mitogen-activated protein kinases in salivary gland adenoid cystic carcinoma

Little is known regarding the mitogen-activated protein kinase activation state in salivary gland adenoid cystic carcinoma. We evaluated the expression of the phosphorylated (activated) forms of the extracellular signal-regulated, C-jun N-terminal, and P38 kinases, as well as the Ki67 index by means of immunohistochemistry in archival paraffin-embedded material in 61 treatment-naive patients. Using a semiquantitative scoring methodology, we found that tumors were heterogeneous in their expression of phosphorylated mitogen-activated protein kinases. The rankings of scores for pairs of phosphorylated kinases across tumors were correlated (P <.01 in all comparisons). The correlation was strongest for phosphorylated P38 and C-jun N-terminal kinases (Kendall's tau, 0.39; 95% confidence interval, 0.21-0.57, P =.0007). Phosphorylated C-jun N-terminal kinases were associated with perineural invasion. In the 55 patients treated by surgery, high phosphorylated P38 (hazard ratio for death, 0.27; 95% confidence interval, 0.10-0.75; P = .01) and Ki67 (hazard ratio for death, 3.86, 95% confidence interval, 1.38-10.77, P =.01) could be used to fit a Cox regression model to overall survival. Our study provides evidence that mitogen-activated protein kinases are activated in adenoid cystic carcinoma and Suggests that their activation is coordinated. High phosphorylated P38 levels predict for overall survival independently of tumor cell proliferation. (C) 2008 Elsevier Inc. All rights reserved.