Expression of
TGFalpha and the
EGF receptor was studied in relation to apoptosis in human colorectal mucosa and premalignant and malignant
tumors. In normal mucosa the
proteins colocalized both in the proliferation compartment and at the
luminal pole of the crypts in cells committed to undergo apoptosis. While staining for the
EGF receptor was increased in premalignant and malignant lesions,
TGFalpha was undetectable in
aberrant crypt foci as well as large areas of
adenomas. Incidence of apoptosis (AI) was high in these areas ranging from 8.83-24.59.
Adenomas did, however, contain islands of high
TGFalpha expression where AI was decreased to a range of 0.76-4.00 (decreased at P=0.0027). In
carcinomas TGFalpha expression was increased above both normal and
adenoma levels corresponding to the decrease in apoptosis in the malignant
tumors. Tissue localization of
TGFalpha and AI were still inversely related ( P=0.022), but interpatient variability was much larger than for
adenomas. The data indicate that
TGFalpha is the main survival factor in premalignant
tumor cells of the colon, while additional factors moderate its effect in
carcinomas. This suggests the possibility of targeting the
EGF receptor pathway not only for treatment but also for the reversal of
adenoma growth and the prevention of malignant
colorectal tumors.