Lack of Thymidylate Synthase by Immunohistochemistry Is Associated with Tumour Downstaging after Preoperative Chemoradiotherapy.
Abstracts
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Preoperative radiotherapy or chemoradiotherapy may reduce local recurrence and improve survival in patients undergoing resection for rectal cancer. Generally patients are selected for preoperative treatment based on clinical and rectal ultrasound staging.Markers of tumour sensitivity to radiotherapy or chemoradiotherapy may aid patient selection. Aim: To evaluate three potential markers (p53;Deleted in Colorectal Cancer (DCC);Thymidylate Synthase (TS))as predictors of pathologic response, local recurrence and survival in patients receiving preoperative adjuvant therapy for rectal cancer. Methods: Patients receiving preoperative adjuvant therapy for locally advanced rectal cancer between 1991 and 1998 were included. Archival tumour specimens were examined by immunohistochemistry (IHC) (p53, DCC and TS) and PCR - single strand conformation polymorphism analysis (PCR-SSCP)(p53 exons 5-8). Results: Seventy-eight patients received preoperative therapy over the study period. Archival tumour samples were available for 60 (25 radiotherapy; 35 chemoradiotherapy).TS IHC negative tumours were more likely to be downstaged by preoperative chemoradiotherapy (TS +ve 32% downstaged, TS -ve 70% p=0.047). The percentage downstaged did not differ significantly between TS IHC +ve and -ve cases in those receiving preoperative radiotherapy alone or in the combined group. Neither p53 IHC or PCR-SSCP nor DCC IHC predicted pathologic response. None of the markers assessed predicted local recurrence or cancer specific survival. Conclusion:TS IHC may help to identify patients with locally advanced rectal cancer who are likely to respond to preoperative chemoradiotherapy. This is consistent with previous reports suggesting that high levels of TS expression are associated with resistance to 5-fluorouracil chemotherapy. |
