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

Adriana Handra-Luca1, Audrey Mauguen, Philippe Ménard

  • 1Service d'Anatomie Pathologique, APHP Hôpital Jean Verdier/GHU Paris 13/Nord, UPRES-EA 3406, Bondy, France. adriana.handra-luca@jvr.aphp.fr

Human Pathology
|July 29, 2008
PubMed

Insights

Mitogen-activated protein kinases are activated in adenoid cystic carcinoma, with coordinated signaling. High phosphorylated P38 levels predict patient survival, independent of tumor proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • The activation state of mitogen-activated protein kinases (MAPK) in salivary gland adenoid cystic carcinoma (ACC) is largely unknown.
  • Understanding MAPK activation is crucial for identifying potential therapeutic targets and prognostic markers in ACC.

Purpose of the Study:

  • To investigate the expression and activation status of key MAPK pathways (ERK, JNK, p38) in treatment-naive ACC.
  • To determine the correlation between MAPK activation, tumor cell proliferation (Ki67), and clinical outcomes, including perineural invasion and overall survival.

Main Methods:

  • Immunohistochemistry was employed to evaluate the expression of phosphorylated (activated) forms of ERK, JNK, and p38 kinases, alongside the Ki67 proliferation index.
  • A cohort of 61 treatment-naive ACC patients' archival paraffin-embedded tissues was analyzed using semiquantitative scoring.
  • Statistical analyses, including correlation assessments and Cox regression modeling, were performed to link molecular findings with clinical data.

Main Results:

  • Tumors exhibited heterogeneous expression patterns of phosphorylated MAPKs, with significant correlations observed between different MAPK activation states.
  • Phosphorylated JNK levels were associated with perineural invasion, a common feature of ACC.
  • High levels of phosphorylated p38 were found to be an independent predictor of improved overall survival in patients treated with surgery, while high Ki67 indicated poorer survival.

Conclusions:

  • MAPK pathways are indeed activated in ACC, and their activation appears to be coordinated.
  • Phosphorylated p38 kinase activation is a significant independent prognostic biomarker for overall survival in ACC patients.
  • These findings highlight the potential role of MAPK signaling in ACC pathogenesis and suggest therapeutic avenues targeting these pathways.

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