title: Co-expression of EGF receptor, TGFalpha and S6 kinase is significantly associated with colorectal carcinomas with distant metastases at diagnosis.
abstract: Autocrine tumour growth factor alpha (TGFalpha)/epidermal growth factor receptor (EGFR) stimulation in colorectal carcinoma (CRC) cells regulates cell adhesion and invasiveness via ribosomal protein S6 kinase (S6K) phosphorylation in pre-clinical studies. The aim of this study was to evaluate whether TGFalpha and EGFR expression might be correlated with a higher metastatic behaviour in human tumours. Paraffin-embedded material was retrospectively collected from 101 primitive CRCs including all stage IV patients at diagnosis treated at our Institution from 1999 to 2004 (50 cases, Group B) and 51 stage II-III control cases (Group A). EGFR and TGFalpha expression, together with signalling molecules (including signal transducer and activator of transcription [STAT3], serine-treonine kinase [Akt], mitogen-activated protein kinase [MAPK], mammalian target of rapamycin [mTOR] and S6K) in selected samples, was evaluated by immunohistochemistry using the EGFR Dako antibody. A total of 68/101 (67.3%) cases were EGFR positive and 79/101 (78.2%) cases were TGFalpha positive. EGFR/TGFalpha co-expression differed significantly (p = 0.02) between Group A and Group B tumours (23/51, 45.1% vs 34/50, 68.0%, respectively), whereas no differences in STAT, Akt, mTOR expression was evident between the two groups. Conversely, there was a significantly higher expression of phosphorylated S6K in stage IV cases (Group B) than in the controls (Group A; 70.4% vs 38.7%; p = 0.02). In agreement with in vitro data, EGFR, TGFalpha and S6K co-expression in human CRC was significantly higher in patients with advanced stage at diagnosis.
authors.affiliation: Division of Medical Oncology, Department of Clinical & Biological Sciences, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano, Turin, Italy. marco.tampellini@unito.it
authors.forename: Marco
authors.initials: M
authors.lastname: Tampellini
authors.forename: Marina
authors.initials: M
authors.lastname: Longo
authors.forename: Susanna
authors.initials: S
authors.lastname: Cappia
authors.forename: Elisa
authors.initials: E
authors.lastname: Bacillo
authors.forename: Irene
authors.initials: I
authors.lastname: Alabiso
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Luigi
authors.initials: L
authors.lastname: Dogliotti
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012189:Retrospective Studies; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016211:Transforming Growth Factor alpha; D011494:Protein Kinases; C546842:MTOR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases