Expression of deoxyuridine triphosphatase (dUTPase) in colorectal tumours

We report the generation of 2 monoclonal antibodies (MAbs), 2B12 and 3E6, s uitable for the detection of human dUTPase in routinely processed paraffin sections by immunohistochemistry. Using these MAbs, we observed nuclear exp ression of dUTPase in the proliferation zones of normal colorectal mucosa a s well as in hyperplastic polyps, Colorectal adenomas and adenocarcinomas r evealed a wide spectrum of dUTPase expression, ranging from 5 to 63% (media n 42%) and from 5 to 71% of tumour cells (median 42%) respectively. Non-par ametric correlation of dUTPase expression with proliferation as determined by a Ki-67 antigen-specific MAb revealed a significant and moderately stron g correlation between proliferation rate and dUTPase expression in adenomas , but not in adenocarcinomas. This finding was confirmed by double-labellin g immunofluorescence. Unexpectedly, we found significantly lower levels of dUTPase expression in primary colorectal carcinomas without lymphnode metas tases at the time of surgery (Dukes A and B stages) than in Dukes C carcino mas. While this observation requires confirmation in larger studies, it sug gests that dUTPase expression may be a negative prognostic marker in colore ctal carcinomas. Moreover, these reagents should prove useful in the contex t 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 ident ifying patients with colorectal carcinomas resistant to adjuvant chemothera py using this and related compounds. Int. J. Cancer (Pred. Oncol.) 84:614-6 17, 1999. (C) 1999 Wiley-Liss, Inc.