IMMUNOHISTOCHEMICAL DETERMINATION OF THYMIDYLATE SYNTHASE IN COLORECTAL-CANCER - METHODOLOGICAL STUDIES

With the aid of specific monoclonal antibodies, an immunohistochemical technique has recently been developed for the detection of intratumor al thymidylate synthase (TS), This technique can be applied to paraffi n-embedded material suitable for retrospective studies. In order to ex amine this technique further, the TS enzyme activity of lysates from f rozen-stored colorectal cancer (CRC) specimens were compared with thei r immunohistochemical TS staining intensity (arbitrarily graded from 0 to 3). A statistically significant correlation between these two meth ods on a total of 25 tumour specimens (P < 0.001) was observed. The st aining intensity in different areas of 48 paraffin-embedded CRCs was e xamined. Sixty-seven per cent of the tumours were homogeneously staine d (either grades 0-1 or 2-3), 33% showed a heterogeneity in TS stainin g. Increased TS expression correlated with more advanced Dukes' stage (P < 0.001). It is concluded that TS immunostaining intensity reflects TS enzyme activity in colorectal tumours and is well suited for paraf fin-embedded material. The TS immunostaining pattern is heterogeneous in up to one-third of the tumours. (C) 1997 Elsevier Science Ltd.