Background: Recent evidence suggests that progressive stages of colorectal tumorigenesis can be defined by a sequence of genetic events characterized by deletion and expression of certain genes and appearance of several oncoproteins. Although the significance of these events is not entirely clear, oncoprotein expression may be directly involved in the tumorigenic mechanism.
Experimental design: We examined the expression of two nuclear oncoproteins, JUN and FOS (Abbreviations used in this paper are lower case letters for oncogenes and upper case letters for oncoproteins), that have not been previously associated with development of colorectal cancer. This study involved detecting p39 c-JUN and p55 c-FOS, as well as two oncoproteins previously known to be expressed during colorectal tumorigenesis, p21 RAS and the tumor suppressor protein, p53. Expression was detected with immunohistochemical methods on formalin-fixed, paraffin-embedded sections of normal human colons, tubular adenomas, tubulovillous adenomas, and adenocarcinomas. Either single oncoprotein expression or coexpression of four selected pairs; RAS/JUN, RAS/FOS, RAS/p53, or JUN/FOS were evaluated.
Results: We found that the expression of all four single oncoproteins and oncoprotein pairs were detected in very few normal colon specimens or tubular adenomas. However, all four oncoproteins and the four oncoprotein pairs were expressed significantly more often in adenocarcinomas. Oncogene expression in tubulovillous adenomas varied with lesion size. The number of lesions expressing any of the four oncoproteins or pairs was not significantly different than normal colon in small (< 1 cm diameter) tubulovillous adenomas. Significantly more large lesions (> 1 cm. diameter) expressed the single oncoproteins RAS, JUN, and FOS than normal colon. Of the four oncoprotein pairs, only RAS/JUN was significantly coexpressed in large tubulovillous adenomas.
Conclusions: We conclude that independent expression of RAS, JUN, and FOS occurred significantly more often in large tubulovillous adenomas and adenocarcinomas while p53 expression occurred primarily in adenocarcinomas. Also, although all four oncoprotein pairs were expressed significantly more often in adenocarcinomas, only RAS/JUN was significantly coexpressed in the large tubulovillous adenomas. These results are comparable with the observed sequential activation of Ki-ras and p53 described by others and suggests that the expression of the nuclear oncogenes, JUN and/or FOS, are also important events in colorectal tumorigenesis.