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.