Identification of molecular markers associated with colorectal
adenoma may uncover critical events involved in the initiation and progression of
colorectal cancer. Our previous studies, mainly based on suppression subtractive hybridization, have identified Reg IV as a strong candidate for a gene that is highly expressed in colorectal
adenoma when compared to normal mucosa. In this study, we sought to determine the
mRNA expression of Reg IV in colorectal
adenoma, in comparison with normal colorectal mucosa and
carcinoma in multiple samples. Semi-quantitative RT-PCR was performed in 12 colorectal
adenomas and 10 concurrent
carcinomas. Reg IV
mRNA level was higher in all
adenomas (12/12) (p=0.001) and in 9/10 concurrent
colorectal carcinoma (p=0.021) when compared to paired normal colorectal mucosa. Northern blot analysis further confirmed these results. In situ hybridization with
digoxigenin (DIG)-labeled
cRNA was performed in 32 colorectal
adenomas with varying degree of dysplasia. Compared with paired normal tissues, Reg IV was overexpressed in 74% (14/19)
adenomas with mild or moderate dysplasia and 100% (13/13) cases of
adenoma with severe dysplasia. In addition, higher levels of Reg IV
mRNA was consistently scored in regions with more severe dysplasia within the same
adenoma sample displaying varying degree of dysplasia. The strongest staining was seen within carcinomoutous areas of the 12
adenoma cases (p=0.002). Our results support that overexpression of Reg IV may be an early event in colorectal
carcinogenesis. Detection of Reg IV overexpression may be useful in the early diagnosis of carcinomatous transformation of
adenoma.