Extra-cellular signal-regulated ERK-1/ERK-2 pathway activation in human salivary gland mucoepidermoid carcinoma: association to aggressive tumor behavior and tumor cell proliferation.
Information on oncogenetic events accompanying salivary gland mucoepidermoid carcinoma is so far limited. Activation of extracellular signal-regulated kinases ERK-1 and ERK-2 is strongly correlated to cancer. Using an antibody specific for phosphorylated (active) ERK-1/ERK-2, we examined human salivary gland mucoepidermoid carcinoma samples by immunohistochemistry. The comparison in paired tumor and normal tissue samples showed that phosphorylated ERK-1/ERK-2 immunoreactivity was higher in tumor cells as compared to surrounding normal salivary parenchyma. ERK-1/ERK-2 phosphorylation was observed in approximately 39% of mucoepidermoid carcinomas. Those tumors where the ERK-1/ERK-2 pathway was activated had a more aggressive tumor behavior as compared to the group where this pathway was inactive. The association of ERK-1/ERK-2 phosphorylation to a worse prognosis was independent of histological grade. ERK-1/ERK-2 phosphorylation was associated with increased Ki67 and cyclin A indexes, which indicated that ERK-1/ERK-2 pathway activation increased tumor cell proliferation. There was no relationship between ERK-1/ERK-2 phosphorylation and HER-2/neu or p16/INK4a protein expression. In conclusion, ERK-1/ERK-2 pathway is active in salivary gland mucoepidermoid carcinoma and this activation is associated to a more aggressive tumor behavior and a higher proliferative activity. These data suggest that deregulation of ERK-1/ERK-2 pathway contributes to mucoepidermoid carcinoma phenotype and, possibly, represents a target for new anticancer drugs.
Handra-Luca
Adriana
A
Service d'Anatomie et de Cytologie Pathologiques, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 83 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
Bilal
Hadi
H
Bertrand
Jacques-Charles
JC
Fouret
Pierre
P
D018277:Carcinoma, Mucoepidermoid / Q000201:enzymology* / Q000473:pathology*; D002455:Cell Division; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000201:enzymology* / Q000473:pathology*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases