TGFalfa, EGFR and p70S6K expression in aggressive colorectal cancer (CRC)

Background: Autocrine TGFa in CRC cells regulates cell adhesion via p70S6K phosphorylation in in vitro studies. The aim was to evaluate whether TGFa expression might be correlated with a higher metastatic behavior in vivo. Methods: 101 primitive CRC tumor samples with paraffin blocks available were retrospectively collected. All the specimens were immunohistochemically evaluated for EGFR clone 2–18C9 (Dako), and TGFa clone 213–4 (Calciochem) expression. A score of 0 to 3 was assigned according to staining intensity and extension. EGFR was also evaluated in randomly selected specimens with clone 111.6 (Neomarks) in 81 cases and clone 31G7 (Zymed) in 28 cases. Selected samples were stained for downstream signalling molecules STAT, p-akt, p-MAP kinase, mTor, p-mTor and p70S6K. Patients were divided into 2 groups according to tumor stage at diagnosis: group A stage II-III (51 pts); group B stage IV (50 pts). Results: EGFR clone 2–18C9 reacted in 68/101 (67.3%) cases. Positivity rates and correlation coefficients were: clone 111.6 42/81 (51.9%), r=0.54 (p<0.01); clone 31G7 20/28 (71.4%), r=0.76 (p<0.0001). TGFa was expressed in 79/101 (78.2%) cases. EGFR and TGFa diffuse staining (score 2, 3) was recorded in 14/51 (27.5%) and 18/51 (35.3%) patients in group A, and 26/50 (52.0%) and 27/50 (54.0%) in group B (p=0.01 and p=0.06). EGFR and TGFa coexpression was evident in 23/51 (45.1%) in group A and in 34/50 (68.0%) in group B (p=0.02). No difference in downstream signaling molecule expression was evident between the 2 groups. A positive correlation trend was recorded for p70S6K which was expressed in 8/20 (40%) and in 8/12 (66.7%) samples of group A and B (p=0.15). Conclusions: EGFR, TGFa and p70S6K expression was more common in patients with advanced stage at diagnosis confirming in vitro data. EGFR scores obtained with commercial antibodies from Zymed and Dako had a significant correlation