Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations

E-cadherin, a transmembrane cell adhesion molecule, has been observed to ha ve an altered pattern of immunoreactivity in several types of carcinomas. I n lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with imm unohistochemistry using the HEC-D1 antibody. Normal protein expression simi lar to that in the adjacent nonmalignant mucosa was seen in 6 cases, wherea s 23 tumours had reduced or absent E-cadherin expression. In the 8 cases wi th no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis f ailed to reveal any cDNA mutations despite the negative immunohistochemistr y. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein proce ssing levels and mutations in other parts of the gene that were not investi gated by the cDNA analysis (e.g. intronic sequences), which could play a ro le in causing abnormal processing of the E-cadherin protein.