title: Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options.
abstract: We analysed the expression of activated (phosphorylated) Akt and MAPK in 98 cases of paired primary colorectal tumours and metastases with the aim to define better the epidermal growth factor receptor (EGFR)-related molecular profile of colorectal cancer as a tool for treatment selection. Among 47 (48%) EGFR-negative primary tumours, 35 cases (74%) were positive for phosphorylated Akt and MAPK. Among 51 (52%) EGFR-positive primary colorectal cancers, 13 (25%) cases were negative for phosphorylated Akt and 15 (29%) were negative for phosphorylated MAPK. In EGFR-negative metastases (56 cases, 55%), phosphorylated Akt was expressed in 41 (73%) and phosphorylated MAPK was expressed in 36 (64%) samples, whereas in EGFR-positive metastases, phosphorylated Akt and MAPK were negative in 14 (31%) and in 10 (22%) cases, respectively. Phosphorylated Akt expression in primary colorectal tumours changed from positive to negative in 16 (16%) paired metastases and from negative to positive in 13 (13%) related metastatic sites. Phosphorylated MAPK expression in primary tumours changed from positive to negative in 13 (13%) paired metastases and from negative to positive in 12 (12%) related metastatic sites. Our findings suggest that phosphorylated Akt and MAPK status in primary tumours does not correlate with Akt and MAPK status in corresponding metastases. EGFR downstream signalling pathway can be overactivated even in the absence of EGFR expression in a considerable proportion of patients.
authors.affiliation: Clinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Via conca 60020, Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Scartozzi
authors.forename: I
authors.initials: I
authors.lastname: Bearzi
authors.forename: R
authors.initials: R
authors.lastname: Berardi
authors.forename: A
authors.initials: A
authors.lastname: Mandolesi
authors.forename: C
authors.initials: C
authors.lastname: Pierantoni
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009362:Neoplasm Metastasis; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3