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2417
Activation of Mitogen-Activated Protein Kinase
(MAPK) Is Associated with Epidermal Growth Factor Receptor (EGFR),
Transforming Growth Factor (TGF)? and HER2 Receptor Overexpression
in Head and Neck Tumors. Federico Rojo, Joan Albanell, Jose
Maria Del Campo, Silvia Sauleda, Guillermo Raspall, Jordi Giralt,
Jose Baselga, Hosp Vall d'Hebron, Barcelona, Spain.
MAPK is a signaling transduction molecule activated by growth
factors receptors that has a critical role in cell growth
regulation. To assess the relationship between activated MAPK and
EGF receptor signaling members (EGFR, activated EGFR, the EGFR
ligand TGFa and HER2 receptor) in human
tumors, specimens from a series of 101 patients with squamous head
and neck cancer were analyzed immunohistochemically. Activated MAPK
was assessed by using an antibody specific for dually phosphorylated
extracellular regulated kinases 1 and 2 that detects the presence of
activated MAPK (phospho-MAPK antibody, NEB) and activated EGFR by an
antibody that specifically reacts with the activated form of the
receptor (Transduction Labs). In 101 paraffin-embedded primary tumor
specimens, 90 collected at the time of diagnosis and 11 after
chemo-radiation therapy, the percentage of tumor cells with nuclei
staining with the phospho-MAPK was: zero in 9 tumors (8.9%), 1-10%
in 21 (20.8%), 11-25% in 44 (43.6%) and > 25% in 27 tumors
(26.7%). A significant relationship was observed between activated
MAPK and EGFR (p=0.037), activated MAPK and TGFa (< 0.001), and activated MAPK and HER2
(p=0.012). The percentage of tumor cells with membrane staining for
the activated EGFR correlated with the percentage of EGFR positive
tumor cells (p<0.0001) but not with expression of TGFa, HER2 or activated MAPK. In 27 patients, specimens
were available before and after chemo-radiation therapy and a
significant decrease in activated MAPK (p><0.001) and
TGFa (p=0.021) was noted. In 19 patients that had a relapse
of their tumors, expression of activated MAPK increased as compared
to pre-therapy specimens (p=0.021). Collectively, these data
indicate that activation of MAPK correlates with expression of
members of the EGFR signaling family in primary head and neck
tumors, is reduced following chemo-radiation therapy, and is
increased in relapsed tumors.
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