Abstract

Objective: Mitogen-Activated Protein (MAP) kinases are involved in both proliferative (via extracellular regulated kinases, ERKs) and apoptotic pathways (via c-jun-N-terminal kinases, JNKs and reactivating kinases, p38/RKs). MAP Kinase Phosphatase-1 (MKP-1) has been shown to dephosphorylate and inactivate all members of the MAP-kinase family. We and others have previously shown that MKP-1, when overexpressed preferentially inhibits apoptotic kinases, and is thus a putative oncogene. Here we evaluate the prognostic significance of MKP-1 expression in Barrett's associated adenocarcinoma.

Methods: 58 cases of Barrett's associated adenocarcinoma, with 612 days of median follow-up were stained for MKP-1 by immunohistochemistry. The same cases were stained for Ki-67 as a measure of proliferation. Statistical analysis was performed by ANOVA for direct comparison of MKP-1 and KI-67, Fisher's exact test for clinicopathological features and by Kaplan-Meier plots for disease-free survival.

Results: MKP-1 was overexpressed in 61% of cases. The remainder expressed MKP-1 in either <25% of tumor cells (11.6%) or were negative. Most of the dysplasias had strong MKP-1 staining. Overexpression of MKP-1 correlated with poor prognosis (p = 0.0245) but not related to proliferative rate (p = 0.2261)

Conclusions: MKP-1 overexpression may be an important marker in the assessment of prognosis and choice of adjuvant therapeutic options in patients with Barrett's associated adenoarcinoma.