We report the generation of 2 monoclonal antibodies (MAbs), 2B12 and 3E6, suitable for the detection of human dUTPase in routinely processed paraffin sections by immunohistochemistry. Using these MAbs, we observed nuclear expression of dUTPase in the proliferation zones of normal colorectal mucosa as well as in hyperplastic polyps. Colorectal adenomas and adenocarcinomas revealed a wide spectrum of dUTPase expression, ranging from 5 to 63% (median 42%) and from 5 to 71% of tumour cells (median 42%) respectively. Non-parametric correlation of dUTPase expression with proliferation as determined by a Ki-67 antigen-specific MAb revealed a significant and moderately strong correlation between proliferation rate and dUTPase expression in adenomas, but not in adenocarcinomas. This finding was confirmed by double-labelling immunofluorescence. Unexpectedly, we found significantly lower levels of dUTPase expression in primary colorectal carcinomas without lymph-node metastases at the time of surgery (Dukes A and B stages) than in Dukes C carcinomas. While this observation requires confirmation in larger studies, it suggests that dUTPase expression may be a negative prognostic marker in colorectal carcinomas. Moreover, these reagents should prove useful in the context of attempts to develop dUTPase inhibitors for cancer chemotherapy. Since it has been demonstrated that dUTPase expression can mediate resistance to 5-fluorouracil, it is also possible that these MAbs may be helpful in identifying patients with colorectal carcinomas resistant to adjuvant chemotherapy using this and related compounds. Int. J. Cancer (Pred. Oncol.) 84:614-617, 1999.
Copyright 1999 Wiley-Liss, Inc.