Association of Epidermal Growth Factor-related Peptides and Type I Receptor Tyrosine Kinase Receptors with Prognosis of Human Colorectal Carcinomas

The frequency of expression and localization of cripto-1 (CR-1),amphiregulin (AR), transforming growth factor alpha (TGF), epidermalgrowth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistryin 45 carcinomas and adjacent non-involved normal colon mucosa.Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%)of the 45 carcinomas showed positive staining for CR-1, AR,TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%),15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involvednormal mucosa specimens were reactive. Among 13 carcinomas withlymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8(61.5%) and 7 (53.8%) exhibited positive staining for CR-1,AR, TGF-, EGFR and erbB-2, respectively. There was a statisticallysignificant association between the frequency of either TGF(P<0.05) or erbB-2 (P<0.05) expression and lymph nodemetastasis. In addition, a signficantly higher frequency ofpositive staining for TGF was observedin Dukes' grade C carcinomas(P<0.05). Finally, significant trends for coexpression ofEGFR and either TGF (P<0.01) or AR (P<0.05) were detectedin carcinomas. These data suggest that AR and TGF may play animportant role in the development of colorectal carcinomas throughan autocrine mechanism involving EGFR, and demonstrate thatTGF and erbB-2 may be more reliable indicators of metastasisor prognosis than CR-1, AR or EGFR in human colon cancers.