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

SummaryLittle 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 τ, 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.