IMMUNOHISTOCHEMICAL DETECTION OF RAS, JUN, FOS, AND P53 ONCOPROTEIN EXPRESSION IN HUMAN COLORECTAL ADENOMAS AND CARCINOMAS

BACKGROUND: Recent evidence suggests that progressive stages of colore ctal tumorigenesis can be defined by a sequence of genetic events char acterized by deletion and expression of certain genes and appearance o f several oncoproteins. Although the significance of these events is n ot entirely clear, oncoprotein expression may be directly involved in the tumorigenic mechanism. EXPERIMENTAL DESIGN: We examined the expres sion of two nuclear oncoproteins, JUN and FOS (Abbreviations used in t his paper are lower case letters for oncogenes and upper case letters for oncoproteins), that have not been previously associated with devel opment of colorectal cancer. This study involved detecting p39 c-JUN a nd p55 c-FOS, as well as two oncoproteins previously known to be expre ssed during colorectal tumorigenesis, p21 RAS and the tumor suppressor protein, p53. Expression was detected with immunohistochemical method s on formalin-fixed, paraffin-embedded sections of normal human colons , tubular adenomas, tubulovillous adenomas, and adenocarcinomas. Eithe r single oncoprotein expression or coexpression of four selected pairs ; RAS/JUN, RAS/FOS, RAS/p53, or JUN/FOS were evaluated. RESULTS: We fo und that the expression of all four single oncoproteins and oncoprotei n pairs were detected in very few normal colon specimens or tubular ad enomas. However, all four oncoproteins and the four oncoprotein pairs were expressed significantly more often in adenocarcinomas. Oncogene e xpression in tubulovillous adenomas varied with lesion size. The numbe r of lesions expressing any of the four oncoproteins or pairs was not significantly different than normal colon in small (<1 cm diameter) tu bulovillous adenomas. Significantly more large lesions (>1 cm. diamete r) expressed the single oncoproteins RAS, JUN, and FOS than normal col on. Of four oncoprotein pairs, only RAS/JUN was significantly coexpres sed in large tubulovillous adenomas. CONCLUSIONS: We conclude that ind ependent expression of RAS, JUN, and FOS occurred significantly more o ften in large tubulovillous adenomas and adenocarcinomas while p53 exp ression occurred primarily in adenocarcinomas. Also, although all four oncoprotein pairs were expressed significantly more often in adenocar cinomas, only RAS/JUN was significantly coexpressed in the large tubul ovillous adenomas. These results are comparable with the observed sequ ential activation of Ki-ras and p53 described by others and suggests t hat the expression of the nuclear oncogenes, JUN and/or FOS, are also important events in colorectal tumorigenesis.