title: Analysis of activated EGFR signalling pathways and their relation to laminin-5 gamma2 chain expression in oral squamous cell carcinoma (OSCC).
abstract: Overexpression of epidermal growth factor receptor (EGFR) was shown for the majority of squamous cell carcinomas. The EGFR expression correlates to tumour size, stage and cytoplasmic accumulation of the laminin-5 gamma2 chain (Ln-5/gamma2), which is known as a marker of invading tumour cells. There is only limited knowledge if and how EGFR signalling pathways are important for invasion-associated processes and for the regulation of Ln-5/gamma2. Therefore the distribution of phosphorylated Erk1/2, p38 MAPK and Akt was immunohistochemically defined in oral squamous cell carcinoma (OSCC) of different histological grade and compared to histological criteria of invasion and cytoplasmic Ln-5/gamma2 deposition. With raising histological grade, there is a slight increase in nuclear pErk1/2-stained tumour cells (P=0.398) and a loss of nuclear (P=0.593) and increased cytoplasmic staining (P=0.144) of pAkt mainly in invading OSCC cells. Nuclear pp38 MAPK could only be sporadically detected in few cases. In case of pErk1/2 and pAkt, only a partial co-localisation could be revealed in cases with abundant kinases and Ln-5/gamma2. Among the investigated kinases, only pAkt shows a relation to histological grade and invasion in OSCC. pErk1/2, pp38 MAPK and pAkt do not represent a direct link between EGFR and Ln-5 synthesis. Therefore, enhanced Ln-5/gamma2 may be a secondary phenomenon of EGFR-induced tumour cell proliferation and dissemination.
authors.affiliation: Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740 Jena, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Richter
authors.forename: Frank D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: Winfried
authors.initials: W
authors.lastname: Hindermann
authors.forename: Laura
authors.initials: L
authors.lastname: Borsi
authors.forename: Peter
authors.initials: P
authors.lastname: Hyckel
authors.forename: Peter
authors.initials: P
authors.lastname: Schleier
authors.forename: Detlef
authors.initials: D
authors.lastname: Katenkamp
authors.forename: Hartwig
authors.initials: H
authors.lastname: Kosmehl
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097794:Kalinin
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000097794:Kalinin; C494918:AKT1 protein, human