Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant metastases and relationship with the clinical response to 5-fluorouracil

Thymidylate synthase (TS) expression in colorectal cancer metastases has be en shown to predict for the clinical response to 5-fluorouracil, Because pr imary tumors may easily provide accessible sources of tissue for marker ana lysis, we have investigated the stability of TS expression between primary colorectal cancer and the corresponding distant metastases and compared the ir relative ability to predict response to chemotherapy on a series of 27 p atients homogeneously treated with biochemically modulated fluorouracil for advanced disease. By immunohistochemistry, high levels of TS expression we re observed in 19 of 27 (70%) primary tumors and in 13 of 27 (48%) metastat ic samples. Overall, TS levels observed in primary tumors did not correlate with those measured in the corresponding metastases (r = 0.30, P = 0.13), with higher TS levels in primary tumors in 8 of 10 discordant cases, Accord ingly, the degree of TS immunoreactivity was significantly higher in primar y tumors compared with the corresponding metastases (mean TS score 3.8; med ian, 4 versus 2.8; median 3; P = 0.001). Response rates after chemotherapy for metastatic disease were similar for patients with low and high TS level s in their primary tumors (37% versus 53%, P = 0.47), In contrast, response rates were 71% and 23% in patients with low and high TS in metastatic samp les (P = 0.012), respectively. In summary, TS levels measured in primary co lorectal cancer do not reflect those observed in the corresponding metastas es and cannot be used to predict their response to chemotherapy, The basis for the higher TS content of primary colorectal cancer compared with the co rresponding metastases needs clarification.